On November 6, 2018 Purdue Pharma L.P. reported that the first patient has been enrolled in a Phase 1 investigator-initiated clinical trial of tinostamustine, an investigational treatment, in patients with newly-diagnosed unmethylated O6-Methylguanine-DNA-methyltransferase (MGMT) glioblastoma multiforme (unmethylated nGBM),1 the most common and aggressive type of primary malignant brain tumor.2 Now open at The University of Texas MD Anderson Cancer Center, the open-label, non-randomized trial will investigate the safety profile, maximum tolerated dose (MTD), and efficacy of tinostamustine (Press release, Purdue Pharma, NOV 6, 2018, View Source [SID1234530936]).

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Glioblastoma is an incurable cancer with a very poor prognosis.2 Median overall survival is only 15 months and survival rates have shown no notable improvement in the past 30 years.3,4 The current standard of care for the disease includes surgery and postoperative radiation therapy with concurrent and adjuvant chemotherapy using temozolomide.5-7 Prognosis is significantly worse for patients with the unmethylated MGMT form of glioblastoma because that tumor type is less likely to respond to currently available treaments.8 Under current standard of care, the two-year overall survival rate was 46 percent in patients with MGMT-methylated nGBM versus 14 percent in patients with unmethylated nGBM.8

"We are excited to see tinostamustine advance into a Phase 1 study in patients with unmethylated glioblastoma multiforme, an extremely aggressive and fatal form of brain tumor," said John Renger, PhD, vice president, Head of Research & Development and Regulatory Affairs, Purdue Pharma. "The limited brain penetration of some medications across the blood-brain barrier contributes to the poor prognosis of this disease, however, preclinical data suggest tinostamustine may have the potential to cross the blood-brain barrier to deliver therapeutic central nervous system concentrations."

The dual-acting therapy candidate tinostamustine, previously known as EDO-S101, is a novel and potentially first-in-class alkylating deacetylase inhibitor (AK-DACi) therapy. Clinical research is underway to evaluate its ability to improve access to and break the DNA strands within cancer cells, and counteract the cancer cells’ attempts to repair the DNA damage.9-12

The potential utility of tinostamustine in the treatment of glioblastoma is supported by various pre-clinical data, and the molecule has shown anti-tumor activity in multiple in-vitro models of glioblastoma. In a pharmacokinetic analysis of tinostamustine administered to murine models by IV bolus and continuous IV infusion (CIVI), tinostamustine crossed the blood-brain barrier with central nervous system (CNS) penetration of 16.5 percent and 13.8 percent for IV bolus and CIVI administrations, respectively.13 CNS penetration with adequate therapeutic CNS concentration is essential for the treatment of brain tumors.

Tinostamustine is an investigational treatment and it is not approved for use in glioblastoma patients. Tinostamustine is also in development for a range of rare or difficult-to-treat blood cancers and advanced solid tumors. The completion of the first-in-human Phase 1 dose escalation study of tinostamustine in patients with relapsed or refractory (difficult-to-treat) hematological malignancies for which there are no available therapies was announced recently, and a Phase 1/2 study in advanced solid tumors was initiated in 2017. Tinostamustine is being developed in the US by Mundipharma EDO on behalf of Purdue Pharma.

To find out more about the study, visit clinicaltrials.gov.

This release discusses an investigational new drug under development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such investigational drug will successfully complete clinical development or receive regulatory approval.

On November 6, 2018 Eidos Therapeutics, Inc. (Eidos) (Nasdaq:EIDX), a clinical stage biopharmaceutical company focused on addressing the large unmet need in transthyretin (TTR) amyloidosis (ATTR), reported its financial results for the quarter ended September 30, 2018 and provided an update on the Company’s recent achievements (Press release, Eidos Therapeutics, NOV 6, 2018, View Source [SID1234576272]).

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"We are working to advance the AG10 clinical development program," said Neil Kumar PhD, chief executive officer of Eidos. "The Phase 1 data demonstrated that AG10 was well tolerated at blood concentrations resulting in near-complete TTR stabilization in healthy volunteers. We are announcing the results from the Phase 2 study in ATTR cardiomyopathy patients at the 2018 American Heart Association Annual Scientific Sessions on November 10, 2018."

Recent Achievements and Upcoming Milestones

Eidos presented Phase 1 data at the 2018 Annual Scientific Meeting of the Heart Failure Society of America, demonstrating that AG10 was well tolerated and establishing clinical proof-of-concept in healthy adult volunteers.

The U.S Food & Drug Administration granted Orphan Drug Designation to AG10 for the treatment of ATTR.

The European Medicines Agency adopted a positive opinion for the designation of AG10 as an orphan medicinal product for the treatment of ATTR.

The Journal of Medicinal Chemistry published the design and preclinical characterization of AG10, demonstrating that AG10’s potentially superior stabilizing activity is driven by the unique ability to mimic the disease-protective T119M mutation and its selectivity for TTR.

The Phase 2 study of AG10 in ATTR cardiomyopathy (ATTR-CM) wild-type and mutant patients with symptomatic heart failure (NYHA Class II-III) concluded and eligible subjects entered a long term, open label extension study.

Eidos will present the Phase 2 data for AG10 in ATTR-CM at the Annual Scientific Sessions of the American Heart Association (AHA) in a late-breaking Featured Science oral presentation on November 10, 2018 at 10am EST. Eidos will also host a conference call and webcast on November 12, 2018 at 8am EST to discuss the results of the Phase 2 trial. Details for the conference call can be found at www.eidostx.com.
Financial Results for the Third Quarter 2018

Cash and cash equivalents totaled $166.6 million at September 30, 2018 compared with $5.5 million at December 31, 2017.

Research and development expenses were $7.9 million for the third quarter of 2018, compared to $2.3 million for the same period of 2017, an increase of $5.6 million. The increase was primarily due to increased expenses for contract consultants, contract manufacturing and other activities for AG10 clinical trials and increases in headcount and related salaries and expenses.

General and administrative expenses were $2.6 million for the third quarter of 2018 compared to $0.5 million for the same period in 2017, an increase of $2.1 million. The increase was primarily due to increased salaries and employee-related expenses and increases in professional fees and services in connection with becoming a public company.

Net loss for the quarter ended September 30, 2018 was $10.2 million or $0.29 per common share, compared to a net loss of $2.8 million or $0.74 per common share for the same period in 2017.

About AG10
AG10 is an orally administered small molecule designed to potently stabilize tetrameric transthyretin, or TTR, thereby halting at its outset the series of molecular events that give rise to amyloidosis, or ATTR. AG10 has completed a Phase 2 clinical trial in patients with ATTR cardiomyopathy and symptomatic heart failure. Results from this trial will be presented on November 10, 2018 at the American Heart Association’s Annual Scientific Sessions.

AG10 was designed to mimic a naturally-occurring variant of the TTR gene (T119M) that is considered a "rescue mutation" because it has been shown to prevent ATTR in individuals also carrying a pathogenic, or disease-causing, mutation in their other copy of the TTR gene. To our knowledge, AG10 is the only TTR stabilizer in development that has been observed to mimic the "super-stabilizing" properties of this rescue mutation that have been well described.

With a pedigree stretching back almost a quarter of a century, BIO-Europe is not only Europe’s largest partnering conference but, according to a recent analysis by 1stOncology™ (also covering BIO International and BIO Asia), it is also one of the world’s richest displays of cancer drug development companies under one roof! With over 600 oncology companies from more than thirty different countries present at BIO-Europe 2018, this is truly a global event. Many of these have also just presented their latest scientific/clinical advancements at the freshly completed European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) (ESMO 2018) congress. Now coming together at the BIO-Europe 2018 meeting they represent more than 5,500 cancer drugs, from discovery to marketed, and are responsible for more than 40% of the world’s current output in cancer R&D, see pipeline breakdown below.

These new cancer drug technologies are being developed from a wide array of organizations, from centuries old universities such as Jagiellonian University (Poland) founded in 1364, to startup companies like Cedilla Therapeutics (USA) and Epigene Therapeutics (Canada), both founded in 2018. Regardless of age they are all coming together at BIO-Europe 2018 to engage with global life science partners.

The global nature of this meeting is revealed when looking at the top nations with cancer drug developing companies present at this year BIO-Europe. It is no surprise to see the United States in first place with 190 companies, UK in second with 48 and Japan is in third place with 41 companies. Please see below table for the top ten nations at BIO-Europe 2018.

In today’s fast moving climate where a company can go from an idea to a public company in a blink of an eye, roughly one third of the 600 cancer companies are publicly traded at various stock exchange markets around the world. No less than seven of these have gone through their initial public offering in 2018 alone, namely ARMO BioSciences, ASLAN Pharmaceuticals, Autolus, BeiGene, Forty Seven, MorphoSys and Sutro Biopharma.

The number of cancer startups, founded in the last five years, present at the BIO-Europe meetings amount to almost fifty, see table below for breakdown per year.

The sizeable cancer pipeline of more than five and a half thousand drugs represented at BIO-Europe is a based on a very diverse selection of technologies and discoveries in cancer biology. Almost one third of these are Immune-Oncology (I-O) drugs including Immune Checkpoint drugs, Cancer vaccines, Bispecific immunomodulators, CAR/TCR therapies and Oncolytic virotherapies, see breakdown by type of I-O drugs below.

In the spotlight of this year’s Nobel Prize in Physiology or Medicine, companies at BIO-Europe feature nearly 300 different immune checkpoint drugs. Other hot progress areas in cancer therapeutics include DNA Damage Response (DDR) drugs, epigenetic therapies, Protein Kinase Inhibitors (PKIs) and Antibody-Dug Conjugates (ADCs).

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On November 5, 2018 Alder BioPharmaceuticals, Inc. (NASDAQ:ALDR), a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, reported its financial results for the third quarter ended September 30, 2018 (Press release, Alder Biopharmaceuticals, NOV 5, 2018, View Source [SID1234530734]).

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"We are pleased to have recently announced the positive results from our pharmacokinetic (PK) comparability study for eptinezumab as we are now in the final stages of compiling the integrated data package for our BLA submission, which continues to be on track for the first quarter of 2019," said Bob Azelby, president and chief executive officer of Alder. "Market research and positive physician feedback have reinforced our confidence in eptinezumab’s encouraging clinical profile, and we believe we are well-positioned to maximize eptinezumab’s potential to treat highly impacted migraine patients."

Recent Company Highlights

Announced positive results from a PK study intended to support the comparability evaluation of the clinical supply for eptinezumab and its planned commercial supply. Both the primary and key secondary PK results met the standard pre-specified acceptance criteria for drug product comparability. Further, the test and reference products were well-tolerated with a similar adverse event profile, and this safety profile was consistent with what has previously been reported for eptinezumab.

Remains on track to complete a robust and integrated BLA submission in the first quarter of 2019, including chemistry, manufacturing, and controls (CMC) processes, positive results from the comparative PK study and data from eptinezumab’s PROMISE 1 and PROMISE 2 pivotal Phase 3 clinical trials, as well as the long-term safety study.

Continued to conduct commercial readiness activities, including expanding the Company’s Medical Science Liaison team; recruiting commercial personnel; and building its reimbursement and distribution services in anticipation of eptinezumab’s potential launch in the first quarter of 2020.

Third Quarter 2018 Financial Results

As of September 30, 2018, Alder had $484.7 million in cash, cash equivalents, investments and restricted cash compared to $536.1 million as of June 30, 2018.

Research and development expenses for the third quarter ended September 30, 2018 totaled $47.8 million, compared to $52.2 million for the same period in 2017. The decrease in expenses was primarily due to lower eptinezumab clinical trial expense as the Company nears completion of patient treatments for several clinical trials, offset by an increase in manufacturing activities and consulting fees to support the planned BLA submission and the production of commercial supply.

General and administrative expenses for the third quarter ended September 30, 2018 totaled $10.7 million, compared to $8.2 million for the same period in 2017. The increase in spending was primarily due to headcount growth and expenses to support commercial readiness activities.

Net loss applicable to common stockholders for the third quarter ended September 30, 2018 totaled $62.2 million, or $0.91 per share, compared to net loss of $59.6 million, or $0.92 per share on a fully-diluted basis, for the same period in 2017.

Financial Outlook

Alder believes its available cash, cash equivalents, investments and restricted cash will be sufficient to meet the company’s projected operating requirements into 2020.

Conference Call and Webcast

Alder will host a conference call today at 5:00 p.m. ET to discuss these financial results and recent corporate highlights. The live call may be accessed by dialing (877) 430-4657 for domestic callers or (484) 756-4339 for international callers and providing conference ID number 9574606. The webcast will be broadcast live and can be accessed from the Events & Presentations page in the Investors section of Alder’s website at www.alderbio.com. The webcast will be available for replay following the call for at least 30 days.

On November 5, 2018 Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS) reported financial results for the quarter ended September 30, 2018 (Press release, Sunesis, NOV 5, 2018, View Source [SID1234530858]). Loss from operations for the three and nine months ended September 30, 2018 was $6.3 million and $20.0 million. As of September 30, 2018, cash and cash equivalents totaled $20.2 million. This capital is expected to fund the company into the second quarter of 2019.

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"We remain focused on advancing our non-covalent BTK inhibitor vecabrutinib to help patients who have developed resistance to covalent BTK inhibitors such as ibrutinib," said Dayton Misfeldt, Interim Chief Executive Officer of Sunesis. "We continue to learn more about this unique asset and its market opportunity and will share an update at the ASH (Free ASH Whitepaper) Annual Meeting in December. As announced last week, one of our accepted abstracts for presentation at ASH (Free ASH Whitepaper) includes an update on the Phase 1b/2 trial of vecabrutinib, and as presented in the published abstract, the pharmacokinetic profile is consistent with the results from our Phase 1a study. We continue to believe that 100mg to 300mg will be the potentially active dose levels. Thus far, vecabrutinib appears well tolerated in the context of advanced disease. We continue with the dose escalation part of the trial and look forward to sharing a complete clinical update at the meeting next month and at a company-sponsored webcast event concurrent with the meeting."

Recent Highlights

Announced Presentations at ASH (Free ASH Whitepaper) Annual Meeting. In November 2018, the Company announced that three presentations will be made at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 1-4, 2018 in San Diego, California. Among the abstracts is an update on the Phase 1b/2 trial of vecabrutinib, titled "Preliminary Safety, Pharmacokinetic, and Pharmacodynamic Results from a Phase 1b/2 Dose-Escalation and Cohort-Expansion Study of the Noncovalent, Reversible Bruton’s Tyrosine Kinase Inhibitor (BTKi), Vecabrutinib, in B-Lymphoid Malignancies," (Publication 3141) which will be presented on Sunday, December 2, in a session titled "CLL: Therapy, excluding Transplantation: Poster II," (Session 642) from 6:00-8:00pm at the San Diego Convention Center, Hall GH. The other poster, titled "Vecabrutinib Is Efficacious In Vivo in a Preclinical CLL Adoptive Transfer Model" will be presented on Saturday, December 1, and an oral presentation "High Prevalence of BTK Mutations on Ibrutinib Therapy after 3 Years of Treatment in a Real-Life Cohort of CLL Patients: A Study from the French Innovative Leukemia Organization (FILO) Group" will be presented in sessions on Monday, December 3. The posters will be available on the Sunesis website following the presentations.

Expanded Clinical Trial Sites. In the third quarter, we added three additional clinical sites to our Phase 1b/2 trial: Memorial Sloan Kettering Cancer Center, Moffitt Cancer Center and University California San Diego. We continue to identify and prepare for adding additional sites as we continue dose escalation and prepare for the Phase 2 expansion portion of the study.

Financial Highlights

Cash and cash equivalents totaled $20.2 million as of September 30, 2018, as compared to $31.8 million in cash, cash equivalents, and marketable securities as of December 31, 2017. This capital is expected to fund the company into the second quarter of 2019. The nine-month decrease of $11.6 million was primarily due to $17.9 million of net cash used in operating activities, partially offset by $6.3 million in net cash flows from financing activities.

Research and development expense was $3.6 million and $11.3 million for the three and nine months ended September 30, 2018, as compared to $6.8 million and $17.9 million for the same periods in 2017, primarily relating to the vecabrutinib and the vosaroxin development program in each period. The decreases of $3.2 million and $6.6 million between the comparable periods from last year was primarily due to a $2.5 million milestone payment made during the third quarter of 2017 to Biogen under the license agreement, a decrease in salary and personnel expenses, a decrease in professional services, and clinical trial expenses related to higher expenses incurred in 2017 due to the MAA with the EMA.

General and administrative expense was $2.7 million and $8.9 million for the three and nine months ended September 30, 2018, as compared to $3.2 million and $10.8 million for the same periods in 2017. The decreases of $0.5 million and $1.9 million between the comparable periods in 2017 were primarily due to reduced professional services, personnel, and commercial expenses.

Interest expense was $0.3 million and $0.9 million for the three and nine months ended September 30, 2018, as compared to $0.3 million and $1.1 million for the same periods in 2017. The decrease during the nine months period was primarily due to the decrease in the outstanding notes payable.

Cash used in operating activities was $17.9 million for the nine months ended September 30, 2018, as compared to $30.8 million for the same period in 2017. Net cash used in the 2018 periods resulted primarily from the net loss of $20.6 million, partly offset by net adjustments for non-cash items of $2.3 million and changes in operating assets and liabilities of $0.4 million. Net cash used in the 2017 period resulted primarily from the net loss of $28.8 million and changes in operating assets and liabilities of $4.6 million, partly offset by net adjustments for non-cash items of $2.6 million.

Loss from operations was $6.3 million and $20.0 million for the three and nine months ended September 30, 2018, as compared to $9.9 million and $28.0 million for the