On March 26, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for TIBSOVO (ivosidenib) in combination with azacitidine for the treatment of newly diagnosed acute myeloid leukemia (AML) with an IDH1 mutation in adult patients who are ≥75 years old or who have comorbidities that preclude use of intensive induction chemotherapy (Press release, Agios Pharmaceuticals, MAR 26, 2019, View Source [SID1234534686]).

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!

"Outcomes for newly diagnosed AML patients ineligible for intensive chemotherapy are still poor, and there are no approved options specifically for patients with an IDH1 mutation," said Chris Bowden, M.D., chief medical officer at Agios. "The Breakthrough Therapy designation provides further support that combining azacitidine and ivosidenib for these patients has the potential to be a compelling treatment option."

The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a drug candidate that is planned to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints.

Results from the Phase 1/2 study of ivosidenib in combination with azacitidine were last presented at the 17th International Symposium on Acute Leukemias in Munich. In the ivosidenib arm of the Phase 1b portion of the study, 23 patients received 500 mg of ivosidenib daily plus azacitidine. The median age was 76 years old, and 52% of patients were age 75 or older. The safety profile of combination therapy remains consistent with the safety profile of ivosidenib and azacitidine alone in this patient population. As of the August 1, 2018 data cutoff, mean neutrophil and platelet counts were maintained near or above thresholds for complete response (CR) with partial hematologic recovery (CRh) while on study treatment with ivosidenib and azacitidine. Overall, 78% (18/23) of patients had a response and 57% (13/23) of patients had a CR. The median duration of CR had not been reached (95% CI 7.7, NE). In addition, the 12-month survival rate was 82%.

Ivosidenib is not approved in any country for the treatment of patients with newly diagnosed AML or approved in combination with azacitidine.

About TIBSOVO (ivosidenib)

TIBSOVO (ivosidenib) is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. For more information, visit TIBSOVO.com.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Patients treated with TIBSOVO have experienced symptoms of differentiation syndrome, which can be fatal if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and hepatic, renal, or multi-organ dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
WARNINGS AND PRECAUTIONS

Differentiation Syndrome: See Boxed WARNING. In the clinical trial, 19% (34/179) of patients with relapsed or refractory AML treated with TIBSOVO experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms of differentiation syndrome in patients treated with TIBSOVO included noninfectious leukocytosis, peripheral edema, pyrexia, dyspnea, pleural effusion, hypotension, hypoxia, pulmonary edema, pneumonitis, pericardial effusion, rash, fluid overload, tumor lysis syndrome, and creatinine increased. Of the 34 patients who experienced differentiation syndrome, 27 (79%) recovered after treatment or after dose interruption of TIBSOVO. Differentiation syndrome occurred as early as 1 day and up to 3 months after TIBSOVO initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. If concomitant noninfectious leukocytosis is observed, initiate treatment with hydroxyurea or leukapheresis, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid and/or hydroxyurea treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt TIBSOVO until signs and symptoms are no longer severe.

QTc Interval Prolongation: Patients treated with TIBSOVO can develop QT (QTc) prolongation and ventricular arrhythmias. One patient developed ventricular fibrillation attributed to TIBSOVO. Concomitant use of TIBSOVO with drugs known to prolong the QTc interval (e.g., anti-arrhythmic medicines, fluoroquinolones, triazole anti-fungals, 5-HT3 receptor antagonists) and CYP3A4 inhibitors may increase the risk of QTc interval prolongation. Conduct monitoring of electrocardiograms (ECGs) and electrolytes. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or in those who are taking medications known to prolong the QTc interval, more frequent monitoring may be necessary.

Interrupt TIBSOVO if QTc increases to greater than 480 msec and less than 500 msec. Interrupt and reduce TIBSOVO if QTc increases to greater than 500 msec. Permanently discontinue TIBSOVO in patients who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.

Guillain-Barré Syndrome: Guillain-Barré syndrome occurred in <1% (2/258) of patients treated with TIBSOVO in the clinical study. Monitor patients taking TIBSOVO for onset of new signs or symptoms of motor and/or sensory neuropathy such as unilateral or bilateral weakness, sensory alterations, paresthesias, or difficulty breathing. Permanently discontinue TIBSOVO in patients who are diagnosed with Guillain-Barré syndrome.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade were fatigue (39%), leukocytosis (38%), arthralgia (36%), diarrhea (34%), dyspnea (33%), edema (32%), nausea (31%), mucositis (28%), electrocardiogram QT prolonged (26%), rash (26%), pyrexia (23%), cough (22%), and constipation (20%).
The most frequently reported ≥Grade 3 adverse reactions (≥5%) were electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), tumor lysis syndrome (6%), and differentiation syndrome (5%).
Serious adverse reactions (≥5%) were differentiation syndrome (10%), leukocytosis (10%), and electrocardiogram QT prolonged (7%). There was one case of progressive multifocal leukoencephalopathy (PML).
DRUG INTERACTIONS

Strong or Moderate CYP3A4 Inhibitors: Reduce TIBSOVO dose with strong CYP3A4 inhibitors. Monitor patients for increased risk of QTc interval prolongation.

Strong CYP3A4 Inducers: Avoid concomitant use with TIBSOVO.

Sensitive CYP3A4 Substrates: Avoid concomitant use with TIBSOVO.

QTc Prolonging Drugs: Avoid concomitant use with TIBSOVO. If co-administration is unavoidable, monitor patients for increased risk of QTc interval prolongation.

LACTATION

Many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with TIBSOVO and for at least 1 month after the last dose.

Please see full Prescribing Information, including Boxed WARNING.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age of diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

On March 26, 2019 Quest Diagnostics (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that it will present results of eight studies at the 2019 American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting, to be held April 2 – 6, 2019 in Seattle, Wash (Press release, Quest Diagnostics, MAR 26, 2019, View Source [SID1234534666]). (Quest Diagnostics booth 929). These studies by Quest Diagnostics researchers evaluate a broad range of laboratory technologies and best practices for aiding in the evaluation of risk for cancer and other diseases.

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!

Among the research is a study that uses a "virtual panel" to estimate genetic disease prevalence in ethnic populations; and a study of associations between certain colorectal cancer genes and risk for breast cancer.

"With so much attention on new therapeutics for cancer and other disorders, people sometimes forget the crucial role of diagnostic insights in guiding treatments to improve outcomes. Genetics and genomics have a greater impact on the treatment and management of cancer and other disorders than ever before," said Felicitas Lacbawan, MD, FCAP, FACMG, Vice President and Executive Medical Director, Advanced Diagnostics Quest Diagnostics. "Quest is delivering diagnostic innovations that provide these insights through its advanced diagnostic services so more people can benefit from new, innovative treatments personalized for them."

A study titled "Anticipated Positive Rates for Genetic Testing in the General Population: a ‘Virtual Panel’ Approach" (Poster 736) evaluates a method for estimating the rate of positivity for multi-gene testing panels in the general population and ethnic sub-populations. The study uses hereditary cancer genes as an example. The level of disease prevalence in a population influences test design and results interpretation. The Quest team developed a method to better predict disease prevalence for inherited cancer genes in ethnic groups, many of which have been traditionally under-represented in genetic testing research.

Another study, "Lynch Syndrome Families with Breast Cancer: Majority of Observed Mutations Are in MSH6 and PMS2," (Poster 220) examined the clinical and family histories of individuals positive for a Lynch syndrome mutation. Lynch syndrome, historically known as hereditary non-polyposis colorectal cancer (HNPCC), is an inherited cancer syndrome associated with a predisposition to colorectal and other cancers. The researchers analyzed the frequency of breast cancer in this population to determine the relationship between Lynch syndrome genes and breast cancer and observed an association with the MSH6 and PMS2 genes. These data, which are in line with previous findings, may help refine breast cancer risk assessment in families with Lynch syndrome, guiding clinical surveillance and management.

Quest is a leader in advanced diagnostics, including the areas of genetic and genomics. The company offers more than 1000 genetic tests, including whole exome sequencing, germline and somatic gene sequencing, noninvasive prenatal screening, pharmacogenomics as well as cytogenetics and biochemical genetic testing. The company’s 650 MDs and PhDs and genetic counselors aid physicians in test selection and interpretation and publish hundreds of studies each year. In Advanced Diagnostics – Genetics, Genomics and R&D alone, there are at least 75 PhDs, MDs and MD/PhDs with 60 board-certified scientific and medical directors.

Abstracts can be accessed on the ACMG website at: View Source;search_type=abstracts&event_id=13

Among the Quest Diagnostics scientific and clinical work being presented at the meeting are:

Double Heterozygotes and Carriers of Biallelic Pathogenic Variants Identified During Genetic Testing for Hereditary Cancer Risk at a Diagnostic Laboratory (Poster: 211)
Lynch Syndrome Families with Breast Cancer: Majority of Observed Mutations Are in MSH6 and PMS2 (Poster 220)
Preliminary Insight from CADASIL Testing: Using Aggregate Patient Data to Correlate Position of Variants in NOTCH3 to Severity of Disease (Poster: 228)
Standards for the Classification and Reporting of Constitutional Copy Number Variants: A ClinGen/ACMG Joint Consensus Recommendation (Poster: 682)
Looming False Negatives: Reconsidering the Clinical Significance of Synonymous Variants (Poster: 705)
Anticipated Positive Rates for Genetic Testing in the General Population: A "Virtual Panel" Approach (Poster 736)
Maternal Chimerism as a Cause of Confounded Gender Reporting and Gender Discordance During cfDNA Screening (Poster: 897)
Confirmatory methods used for germline NGS Testing Teach Us About the Strengths and Weaknesses of Molecular Technologies (Poster: 8781)

On March 26, 2019 Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZS) reported its financial and operating results for the fourth quarter and year ended December 31, 2018 (Press release, AEterna Zentaris, MAR 26, 2019, View Source [SID1234534653]).

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!

All Amounts are in U.S. Dollars

Highlights

Total revenue for fiscal 2018 was $26.9 million, compared to $0.9 million for fiscal 2017

Income from operations for fiscal 2018 was $9.8 million, compared to a loss from operations of $23.1 million for fiscal 2017

Net income for fiscal 2018 was $4.2 million, compared to a net loss of $16.8 million for fiscal 2017

Total revenue for Q4 2018 was $1.4 million, compared to $0.2 million for Q4 2017

After our year-end, in January 2019, European Medicines Agency (EMA) granted marketing authorization for macimorelin for diagnosis of adult growth hormone deficiency

As of December 31, 2018, we had $14.5 million of unrestricted cash and cash equivalents
Summary of Full-Year Results

For the year ended December 31, 2018, we reported a consolidated net income of $4.2 million, or $0.25 per common share, as compared with a consolidated net loss of $16.8 million, or $1.12 loss per common share, for the year ended December 31, 2017. The $21 million improvement in results arose primarily from a $23.9 million increase in gross profit (which resulted primarily from the $24 million royalty payment received from Strongbridge Biopharma) and a $9.1 million reduction in operating expenses. These improvements were offset in part by the $5.55 million in tax expense in 2018 (compared to a tax recovery in 2017 of $3.5 million) and $1.6 million decrease in net finance income.

Revenues

Our total revenue for the year ended December 31, 2018 was $26.9 million as compared with $0.9 million for the same period in 2017, representing an increase of $26.0 million. The 2018 revenue comprised $24.3 million in license revenue, $2.2 million in product sales, $0.2 million in royalty income and $0.2 million in sales commissions as compared with $0.4 million in license fee and $0.5 million in license fees in 2017. The increase in total revenue in 2018 relates to license fees, royalty income and product sales associated with executing the License and Assignment Agreement for Macrilen (macimorelin) in January 2018.

Cost of sales

Our total cost of goods sold for the year ended December 31, 2018 was $2.1 million as compared with nil for the same period in 2017, reflecting the costs of our sales of Macrilen (macimorelin) inventory pursuant to an interim supply agreement under the License and Assignment Agreement.

Operating Expenses

Our total operating expenses for the year ended December 31, 2018 was $14.9 million as compared with $24.0 million for the same period in 2017, representing a decline of $9.1 million. This was primarily due to a $7.8 million decline in research and development costs, while the $2.0 million decrease in selling expenses was offset by $0.1 million increase in general and administrative expenses.

In 2018, our focus was on our PIP study for Macrilen (macimorelin), for which we received $0.4 million from our licensee for its share of such costs.

Our general and administrative expenses were higher in 2018 than expected as we incurred significant legal costs in the course of reaching settlement agreements for $1.4 million.

Our selling expenses are in-line with expectations and lower in 2018 than in 2017 due to the Q1 2018 termination of our North American sales team and our co-promotion activities as we shifted our focus to licensing Macrilen (macimorelin).

Net Finance Income

Our net finance income for the year ended December 31, 2018 was $1.2 million, as compared to $2.8 million for the same period in 2017, representing a decrease of $1.6 million. The decline in net finance income is primarily due to the change in fair value of our warrant liability. Such change in fair value results from the periodic "mark-to-market" revaluation via the application of pricing models to our outstanding share purchase warrants.

Summary of Fourth Quarter Results

For the three-month period ended December 31, 2018, we reported a consolidated net loss of $5.1 million, or $0.31 loss per common share, as compared with a consolidated net loss of $0.5 million, or $0.03 loss per common share, for the three-month period ended December 31, 2017. The $4.6 million increase in net loss in 2018, as compared with 2017, results primarily from $2.8 million in tax expense movement, $1.4 million increase in cost of goods, $0.9 million increase in finance costs and $0.8 million increase in settlements, offset by $1.2 million increase in total revenues. In the fourth quarter of 2018, unlike in 2017, we earned $0.2 million in royalty income from our licensee and expensed $0.8 million in one-time settlement costs to settle a lawsuit against the Company from two of our former executives. In the fourth quarter of 2018 we also actively began the EMA and FDA pediatric study for Macrilen (macimorelin).

Consolidated Financial Statements and Management’s Discussion and Analysis

For reference, the Management’s Discussion and Analysis of Financial Condition and Results of Operations for the fourth quarter and fiscal 2018, as well as the Company’s audited consolidated financial statements as at December 31, 2018, 2017 and for the years ended December 31, 2018, 2017 and 2016 will be available at www.zentaris.com in the "Investors" section or at the Company’s profile at www.sedar.com and www.sec.gov.

Annual and Special Meeting of Shareholders

The Company has scheduled its annual shareholders meeting for 10:00 am (Eastern time) on May 8, 2019 at 1155 René-Lévesque Blvd. West, 41st Floor, Montreal, Quebec. At that meeting, in addition to the presentation of the Company’s annual financial statements, the election of directors and the appointment of the Company’s auditors, shareholders will also consider resolutions to move the Company’s registered address from Quebec to Ontario, and to renew and amend the Company’s existing shareholders rights plan. These matters are described in detail in the Company’s 2019 Management Proxy Circular. This proxy circular and a copy of the proposed amended and restated shareholders rights plan will be available at www.sedar.com and www.sec.gov.

At the Company’s 2019 annual and special meeting, the Company will be proposing that the size of its board of directors be reduced from seven to five, with Mr. Mike Cardiff having resigned from the board of directors for personal reasons in March 2019 and Mr. Juergen Ernst having indicated to the Company his desire not to be nominated for re-election. The Company thanks both of them for their service to the Company.

On March 26, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported that it intends to offer and sell units consisting of shares of common stock and warrants in an underwritten public offering (Press release, Moleculin, MAR 26, 2019, View Source [SID1234534647]). All units in the offering will be sold by Moleculin. The proposed offering is subject to market and other conditions. There can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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!

Oppenheimer & Co. Inc. is acting as the sole book-running manager for the proposed offering.

The Company intends to use the net proceeds of the offering to fund its planned clinical trials, preclinical programs, for other research and development activities and for general corporate purposes.

The securities described above are being offered by the Company pursuant to a shelf registration statement on Form S-3 (No. 333-219434) previously filed with and declared effective by the Securities and Exchange Commission (SEC). A preliminary prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus may be obtained, when available, from Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, New York 10004, by telephone at (212) 667-8055, or by email at [email protected]. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the SEC.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On March 26, 2019 Abcuro, Inc., a biopharmaceutical company developing first-in-class immunomodulatory therapeutics, reported the publication of proof-of-concept data describing KLRG1 as a promising new target for cancer immunotherapy (Press release, Abcuro, MAR 26, 2019, View Source [SID1234534646]). The article, published in Oncotarget ( link ), reports the anticancer activity of KLRG1 antibody blockade in syngeneic mouse models of breast cancer, colon cancer and melanoma. The study also highlights the expression of KLRG1 in human tumor infiltrating lymphocytes (TILs) and its role in adaptive resistance to immunotherapies.

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!

KLRG1 was identified as a critical immune inhibitory receptor by datamining expression profile databases with the aim of finding immune checkpoint receptors that align with the state of T cell differentiation. This analysis showed that KLRG1 is, genome wide, the immune inhibitory receptor that best aligns with degree of T cell differentiation. Compared to other clinical targets that are active in early and intermediate stages of T cell differentiation (such as CTLA-4 and PD-1), KLRG1 functions as the ultimate break on the most differentiated and cytotoxic T cells. Furthermore, KLRG1 expression on a differentiated subset of T cells and the high cytotoxic potential of these cells strongly suggests a beneficial therapeutic combination with existing treatments.

The results presented in the publication show in vivo proof-of-concept for the anti-cancer action resulting from KLRG1 blockade in mouse syngeneic models and highlight KLRG1 as an important driver of adaptive resistance to immunotherapy in humans. Abcuro has discovered KLRG1 blocking antibodies and is developing first-in-class new immunotherapy agents for treatment of cancer.