On May 2, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to update the U.S. Prescribing Information for TIBSOVO, an isocitrate dehydrogenase-1 (IDH1) inhibitor, to include adult patients with newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by an FDA-approved test who are ³ 75 years old or who have comorbidities that preclude use of intensive induction chemotherapy (Press release, Agios Pharmaceuticals, MAY 2, 2019, View Source [SID1234535563]). The sNDA was granted Priority Review and accepted under the FDA’s Real-Time Oncology Review pilot program, which aims to make the review of oncology drugs more efficient by allowing the FDA access to clinical trial data before the information is formally submitted to the agency. TIBSOVO received initial FDA approval in July 2018 for adult patients with relapsed or refractory (R/R) AML and an IDH1 mutation1.

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!

"Despite several new AML medicines approved in the last two years, many newly diagnosed patients are still not eligible for existing therapies or combination regimens because of age and other comorbidities," said Chris Bowden, M.D., chief medical officer at Agios. "With today’s additional TIBSOVO approval, we are now able to provide a targeted, oral therapy to patients with an IDH1 mutation who may not have other treatment options. In addition, we are continuing our work to expand the utility of TIBSOVO in newly diagnosed AML patients in ongoing Phase 3 trials in combination with both intensive chemotherapy and azacitidine. I would like to thank the patients, nurses, physicians and caregivers who participated in the clinical trial, as well as the tremendous employees at Agios whose focus on patients made this possible."

AML is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases estimated in the U.S. each year2,3. AML patients are typically older or have comorbidities that preclude the use of intensive chemotherapy4. These patients typically have a worse prognosis and poor outcomes5. The majority of patients with AML eventually relapse6. The five-year survival rate is approximately 28%2. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia7. IDH1 mutations have been associated with negative prognosis in AML8,9.

LOGO

"The Phase 1 results for TIBSOVO demonstrated that this oral, single agent therapy can induce durable responses in newly diagnosed AML patients with an IDH1 mutation," said Gail J. Roboz, M.D., Professor of Medicine, Director of the Leukemia Program and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center*. "Many patients included in the study had features associated with particularly aggressive and challenging forms of AML, including secondary disease, adverse risk genetics and prior treatment with hypomethylating agents."

TIBSOVO Safety and Efficacy Data1

The efficacy of TIBSOVO was evaluated in an open-label, single-arm, multicenter clinical trial

(Study AG120-C-001, NCT02074839) that included 28 adult patients with newly diagnosed AML with an IDH1 mutation who were assigned to receive a 500 mg daily dose. The cohort included patients who were age 75 or older or had comorbidities that precluded the use of intensive induction chemotherapy (baseline Eastern Cooperative Oncology Group [ECOG] performance status of ³2, severe cardiac or pulmonary disease, hepatic impairment with bilirubin >1.5 times the upper limit of normal, or creatinine clearance <45 mL/min). Patients had a median age of 77 years (range of 64 to 87) and 68% had AML with myelodysplasia-related changes. The primary endpoint is the combined complete remission (CR) and complete remission with partial hematologic improvement (CRh) rate. CRh is defined as <5% of blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts (platelets >50,000/microliter and ANC >500/microliter).

In this trial, TIBSOVO demonstrated:

•
CR+CRh rate of 42.9% (12 of 28 patients) (95% CI: 24.5, 62.8).

•
The CR rate was 28.6% (8 of 28 patients) (95% CI 13.2, 48.7) and the CRh rate was 14.3% (4 of 28 patients) (95% CI 4.0, 32.7).

•
Median durations of CR and CR+CRh were not estimable, with 5 patients (41.7%) who achieved CR or CRh remaining on TIBSOVO treatment (treatment duration range: 20.3 to 40.9 months) as of the data cutoff.

•
58.3% (7 of 12) of patients who achieved CR or CRh were in remission at 1 year after receiving treatment.

•
For patients who achieved a CR or CRh, the median time to best response of CR or CRh was 2.8 months (range, 1.9 to 12.9 months).

•
Among the 17 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 7 (41.2%) became independent of RBC and platelet transfusions during any 56-day post-baseline period.

•
Of the 11 patients who were independent of both RBC and platelet transfusions at baseline, 6 (54.5%) remained transfusion independent during any 56-day post-baseline period.

LOGO

The safety profile of single-agent TIBSOVO was evaluated in 28 patients with newly diagnosed AML with an IDH1 mutation treated with a dose of 500 mg daily. The median duration of exposure to TIBSOVO was 4.3 months (range, 0.3 to 40.9 months). In the clinical trial, 25% (7 of 28) of patients treated with TIBSOVO experienced differentiation syndrome, which can be fatal if not treated. Of the 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. QTc interval prolongation occurred in patients treated with TIBSOVO. The most common adverse reactions (³20%) of any grade in patients with newly diagnosed AML were diarrhea, fatigue, decreased appetite, edema, nausea, leukocytosis, arthralgia, abdominal pain, dyspnea, myalgia, constipation, differentiation syndrome, dizziness, electrocardiogram QT prolonged, mucositis and vomiting.

About TIBSOVO (ivosidenib)

TIBSOVO is indicated for the treatment of acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in:

•
Adult patients with newly-diagnosed AML who are ³75 years old or who have comorbidities that preclude use of intensive induction chemotherapy.

•
Adult patients with relapsed or refractory AML.

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, 25% (7/28) of patients with newly diagnosed AML and 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 7 patients with newly diagnosed AML who experienced differentiation syndrome, 6 (86%) patients recovered. Of the 34 patients with relapsed or refractory AML who experienced differentiation syndrome, 27 (79%) patients 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.

LOGO

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, or 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 including laboratory abnormalities (³20%) were hemoglobin decreased (60%), fatigue (43%), arthralgia (39%), calcium decreased (39%), sodium decreased (39%), leukocytosis (38%), diarrhea (37%), magnesium decreased (36%), edema (34%), nausea (33%), dyspnea (32%), uric acid increased (32%), potassium decreased (32%), alkaline phosphatase increased (30%), mucositis (28%), aspartate aminotransferase increased (27%), phosphatase decreased (25%), electrocardiogram QT prolonged (24%), rash (24%), creatinine increased (24%), cough (23%), decreased appetite (22%), myalgia (21%), constipation (20%), and pyrexia (20%).

In patients with newly diagnosed AML, the most frequently reported Grade ³3 adverse reactions (³5%) were fatigue (14%), differentiation syndrome (11%), electrocardiogram QT prolonged (11%), diarrhea (7%), nausea (7%), and leukocytosis (7%). Serious adverse reactions (³5%) were differentiation syndrome (18%), electrocardiogram QT prolonged (7%), and fatigue (7%). There was one case of posterior reversible encephalopathy syndrome (PRES).

In patients with relapsed or refractory AML, the most frequently reported Grade ³3 adverse reactions (³5%) were differentiation syndrome (13%), electrocardiogram QT prolonged (10%), dyspnea (9%), leukocytosis (8%), and tumor lysis syndrome (6%). Serious adverse reactions (³5%) 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

Because 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 is a cancer of the blood and bone marrow marked by rapid disease progression and is the most common acute leukemia affecting adults with approximately 20,000 new cases estimated in the U.S. each year2,3. AML patients are typically older or have comorbidities that preclude the use of intensive chemotherapy4. These patients typically have a worse prognosis and poor outcomes5. The majority of patients with AML eventually relapse6. The five-year survival rate is approximately 28%2. For 6 to 10 percent of AML patients, the mutated IDH1 enzyme blocks normal blood stem cell differentiation, contributing to the genesis of acute leukemia7. IDH1 mutations have been associated with negative prognosis in AML8,9.

About myAgios Patient Support Services

myAgios Patient Support Services is an expansive program that helps patients with access, reimbursement, and financial assistance for TIBSOVO (ivosidenib). Healthcare providers and pharmacists can enroll patients at myAgios.com/enroll.

On May 2, 2019 Cambrex Corporation (NYSE: CBM), the leading small molecule company providing drug substance, drug product and analytical services across the entire drug lifecycle, reported results for the first quarter ended March 31, 2019 (Press release, Cambrex, MAY 2, 2019, View Source [SID1234535561]).

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!

First Quarter 2019 Highlights

Completed the acquisition of Avista Pharma Solutions ("Avista"), an early clinical phase contract development, manufacturing and testing organization, for approximately $252 million in total cash consideration. This transaction closed on January 2, 2019.

Net revenue was $159.5 million, an increase of 13% compared to the same quarter last year. Excluding the impact of currency, net revenue increased 17%.

Income from continuing operations was $10.5 million and Diluted EPS was $0.31 per share compared to $24.2 million and $0.72 per share, respectively, for the same quarter last year. Adjusted Income from continuing operations and Diluted EPS were $20.2 million and $0.60 per share compared to $25.8 million and $0.77 per share, respectively, for the same quarter last year (see table at the end of this press release).

Adjusted EBITDA was $41.1 million compared to $37.9 million in the same quarter last year (see table at the end of this press release).

Net debt excluding lease obligations was $430.0 million at the end of the quarter compared to $204.1 million at December 31, 2018. The change during the quarter was primarily the result of acquiring Avista and related expenses, positively offset by $28.7 million of Free cash flow. The Company entered into an $800 million amended credit facility in January of 2019 in connection with the Avista acquisition.

The Company continues to expect full year 2019 Net revenue, which excludes the impact of foreign currency, to be between 21% and 25% higher than 2018 Net revenue. Adjusted EBITDA is still expected to be between $150 and $160 million (see Financial Expectations – Continuing Operations section below for related explanations and additional financial guidance).

"The first quarter was a very productive quarter for Cambrex. Our financial performance was in line with our full year expectations, and we saw many examples of the synergies we anticipated when we acquired Halo and Avista. While there is still much work to be done, we took significant steps towards realizing our vision of building the leading fully integrated global small molecule CDMO. As our commercial team gains experience selling all of our services, and awareness of the full scope of our offering grows with existing and prospective customers, we expect the synergies to become more and more significant moving forward," commented Steven M. Klosk, President and Chief Executive Officer.

"We continue to invest in our facilities to ensure we have world class capabilities that position us to take advantage of ongoing positive CDMO market trends. During the quarter, we announced several new investments in our business including expanded cGMP liquid filling capacity at our Mirabel, Quebec facility, and expanded laboratories to facilitate increased generic API development capabilities at our site outside of Milan, Italy. In April, we completed construction of a new production area to manufacture highly potent drug substances at our Charles City, Iowa facility, and expect to begin production during the second quarter of 2019."

Basis of Reporting

The Company has provided a reconciliation of GAAP to adjusted (i.e. Non-GAAP) amounts at the end of this press release. Cambrex management believes that the adjustments provide useful information to investors due to the magnitude and nature of certain amounts recorded under GAAP.

As a result of the recent Halo and Avista acquisitions and consistent with how the business is managed, the Company has three reportable segments, Drug Substance ("DS"), which includes the legacy Cambrex API business excluding the High Point, North Carolina facility, Drug Product ("DP"), which includes the former Halo business, and Early Stage Development and Testing ("ESDT"), which includes the former Avista business in addition to the High Point facility.

First Quarter 2019 Operating Results – Consolidated, Continuing Operations

Net revenue was $159.5 million, an increase of $18.4 million, or 13%, from $141.1 million in the same quarter last year. Results include a 4% unfavorable impact of foreign exchange compared to the first quarter of 2018. Net revenue during the first quarter of 2019 includes the acquisitions of Halo and Avista. Compared to the same quarter last year, the Drug Substance segment revenues declined due to lower volumes.

Gross margin was 34% for the first quarter of 2019 compared to 36% in the same quarter last year.

Operating profit was $20.3 million for the first quarter of 2019 compared to $30.4 million in the same quarter last year. Operating profit for 2019 includes a $4.2 million increase in amortization expense for purchased intangibles and $6.1 million in acquisition and integration expenses. Adjusted EBITDA was $41.1 million compared to $37.9 million in the same quarter last year (see table at the end of this press release).

Income tax expense was $3.5 million resulting in an effective tax rate of 25% compared to $5.8 million and an effective tax rate of 19% in the same quarter last year. Income tax expense for the first quarter of 2018 would have been approximately 20% excluding the immediate recognition of certain effects of share-based compensation. The increase in the tax rate for 2019 as compared to 2018 is primarily due to higher state taxes as a result of state tax reform and the Company’s expanded state tax presence due to recent acquisitions, as well as the geographic mix of income.

`

Income from continuing operations was $10.5 million, or $0.31 per diluted share, compared to $24.2 million, or $0.72 per diluted share, in the same quarter last year.

Adjusted Income from continuing operations was $20.2 million, or $0.60 per share, compared to $25.8 million, or $0.77 per share, in the same quarter last year.

Capital expenditures were $19.2 million and depreciation and amortization was $14.7 million compared to $23.8 million and $7.5 million, respectively, in the same quarter last year.

Net debt was $430.0 million at the end of the quarter compared to $204.1 million at December 31, 2018. The change during the quarter was primarily the result of acquiring Avista and related transaction and integration expenses, positively offset by $28.7 million of Free cash flow.

First Quarter 2019 Operating Results – Drug Substance ("DS") segment

Net revenue was $112.1 million compared to $136.6 in the same quarter last year, an 18% decrease. This includes a 4% unfavorable impact of foreign exchange compared to the first quarter of 2018. The decrease was due to lower volumes of certain branded APIs, primarily from Cambrex’s largest product, partially offset by higher sales of clinical phase products and generic APIs.

Gross profit in the first quarter of 2019 was $43.4 million compared to $50.0 million in the same quarter last year. Gross margin increased to 39% from 37% in the same quarter last year. The increase in margin was primarily driven by a favorable impact from foreign currency, favorable product mix related to generic APIs and lower inventory charges due to batch failures in 2018 partially offset by lower production volumes.

Selling, general and administrative ("SG&A") expenses were $9.4 million in the first quarter of 2019 compared to $11.5 million in the same quarter last year. The decrease was mainly due to lower consulting costs associated with a 2018 operational excellence initiative and the impact of foreign currency.

Operating profit was $31.2 million compared to $35.4 million in the first quarter of 2018. The decrease was due to lower gross profit partially offset by lower operating expenses as described above.

First Quarter 2019 Operating Results – Drug Product ("DP") segment

Net revenue in the first quarter of 2019 was $24.5 million. The former Halo business that comprises what is now the DP segment was acquired in September of 2018.

Gross profit was $6.0 million and gross margin was 25% in the first quarter of 2019.

SG&A expenses were $6.2 million in the first quarter of 2019, which includes amortization of purchased intangibles of $3.0 million.

Operating loss was $0.3 million in the first quarter of 2019 which includes amortization of purchased intangibles of $3.0 million.

`

First Quarter 2019 Operating Results – Early Stage Development and Testing ("ESDT") segment

The Company’s Cambrex High Point ("CHP") facility is included in the ESDT segment for both periods presented. The former Avista businesses that comprise the majority of what is now the ESDT segment were acquired in January of 2019. The 2018 results for this segment include only the High Point facility, formerly part of Cambrex’s legacy API business.

Net revenue in the first quarter of 2019 was $22.9 million compared to $4.5 million in the same quarter last year. The increase is due to the acquisition of Avista and a 31% increase in CHP’s first quarter 2019 revenue.

Gross profit was $5.5 million in the first quarter of 2019 compared to $0.9 million in the same quarter last year. Gross margin was 24% in the first quarter of 2019 compared to 20% in the same period last year.

SG&A expenses were $6.5 million in the first quarter of 2019, which includes amortization of purchased intangibles of $1.4 million.

Operating loss was $2.5 million in the first quarter of 2019, which includes $1.2 million in integration expenses and $1.4 million of amortization of purchased intangible assets. Operating loss for the first quarter of 2018 was $0.4 million.

First Quarter 2019 Operating Results – Corporate Headquarters

SG&A expenses were $2.9 million in the first quarter of 2019 compared to $4.0 million in the same quarter last year. The decrease is primarily the result of lower due diligence costs related to mergers and acquisition activities.

Consolidated acquisition and integration expenses were $6.1 million for the first quarter of 2019, of which $4.9 million is reflected in the Corporate Headquarters cost center and $1.2 million is reflected in the ESDT segment. There were no acquisition and integration expenses during the first quarter of 2018.

Operating loss at Corporate in the first quarter of 2019 was $8.1 million compared to $4.6 million in the same quarter last year.

Financial Expectations – Continuing Operations

The following table shows the Company’s current expectations for its full year 2019 financial performance versus its expectations from the previous quarter. The expectations in the table below reflect expected results from the business including the recent acquisitions of Halo and Avista. All expectations for 2019, including growth relative to 2018, are based on actual and expected ASC 606 results for both years.

Consistent with the Company’s usual guidance practices, these financial expectations are for continuing operations and exclude the impact of any potential future acquisitions and related transaction and integration expenses, including expenses related to the recent acquisitions of Halo Pharma and Avista Pharma Solutions, divestitures, restructuring activities, certain tax items discussed below, and the impact of foreign currency on Net revenue.

EBITDA, Adjusted EBITDA and Adjusted Income from continuing operations per share for 2019 will be computed on a basis consistent with the reconciliation of the current quarter financial results in the tables at the end of this press release. Free cash flow is defined as the change in debt (excluding lease obligations, M&A and integration expenses), net of cash during the year. Adjusted effective tax rate excludes the immediate recognition of certain benefits of share-based compensation and certain other items adjusted for in the non-GAAP reconciliation tables at the end of this release.

The tax rate will be sensitive to the Company’s geographic mix of income, changes in the tax laws or rates within the countries in which the Company operates and the effects of certain share-based payments.

Cambrex expects M&A and related integration expenses for 2019 to be between $9 and $11 million. These amounts are excluded from the guidance for consolidated Adjusted EBITDA, Adjusted income from continuing operations per share and Free cash flow included above. These expenses include approximately $3.8 million of transaction and $2.3 million of integration expenses incurred in conjunction with the acquisition of Avista in early January and expected on-going integration expenses across most functional areas for the remainder of 2019. This estimate also includes certain anticipated expenses related to IT systems, but does not include costs to upgrade the two newly acquired businesses to Cambrex’s ERP software, which are planned to occur over the course of 2019 and 2020.

Expectations above include preliminary estimates for Depreciation and Amortization expense associated with purchase accounting for the Avista acquisition. Cambrex expects to finalize the purchase accounting for Avista during the second quarter of 2019. As a result, expected Depreciation and Amortization expense and its impact on expected Adjusted income from continuing operations per share in the table above could change when purchase accounting is finalized.

Refer to the tables at the end of this press release which include items typically adjusted to arrive at the Company’s non-GAAP results.

The financial information contained in this press release is unaudited, subject to revision and should not be considered final until the Company’s Form 10-Q for first quarter 2019 is filed with the Securities and Exchange Commission ("SEC").

Conference Call and Webcast

A conference call to discuss the Company’s first quarter 2019 results will begin at 8:30 a.m. Eastern Time on May 2, 2019 and can be accessed by calling 1-800-682-0995 for domestic and +1-334-323-0522 for international. Please use the passcode 2251796 and call approximately 10 minutes prior to the start time. A webcast will be available in the Investors section on the Cambrex website located at www.cambrex.com. A telephone replay of the conference call will be available through May 9, 2019 by calling 1-888-203-1112 for domestic and +1-719-457-0820 for international. Please use the passcode 2251796 to access the replay.

On May 2, 2019 GlycoMimetics, Inc. (Nasdaq: GLYC) reported its financial results for the first quarter ended March 31, 2019 and highlighted recent company achievements (Press release, GlycoMimetics, MAY 2, 2019, View Source [SID1234535557]). Quarter-end cash was $195.6 million.

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!

"The first quarter of 2019 was one of focused activity in the clinical development arena. We continued to identify and initiate new sites and enroll participants in our Company-sponsored Phase 3 trial in relapsed or refractory AML patients. We also worked closely with our two consortia partners to expand our late-stage uproleselan program, culminating in our announcement that the NCI consortium dosed its first patient in its trial in late April. During the same period, we worked with clinical collaborators at Duke Cancer Institute to plan our next trial for GMI-1359, a dual antagonist of E-selectin and CXCR-4, and defined individuals with breast cancer and bone metastases as our initial target study population," said Rachel King, GlycoMimetics Chief Executive Officer.

Key First-Quarter 2019 and Recent Operational Highlights:

The GlycoMimetics-sponsored pivotal Phase 3 trial of uproleselan in relapsed/refractory AML continues to enroll patients in the US and Australia. Clinical sites across the US, Europe, Canada and Australia continue to be identified and activated.

The NCI-sponsored clinical trial evaluating uproleselan in newly diagnosed older adults with AML has initiated enrollment.

Study start-up activities continued for the collaborative Haemato Oncology Foundation for Adults in the Netherlands (HOVON) European study of uproleselan in newly diagnosed patients unfit for chemotherapy.

The Company announced plans to initiate a proof-of-concept clinical trial of GMI-1359 in individuals with breast cancer whose tumors have spread to bone. The trial will evaluate safety and biomarkers of cancer cell mobilization in individuals with hormone receptor positive metastatic breast cancer.

Data was published in Nature Cell Biology that strongly suggests that E-selectin is key to tumor growth and metastasis to bone and provides further support for the upcoming clinical trial of GMI-1359 in individuals with metastatic breast cancer.

Dr. Eric Feldman has joined the GlycoMimetics executive team as Vice President, Clinical Development, and Christian Dinneen-Long has joined as Vice President, Corporate Counsel.

A planned transition is taking place within the Company’s Board of Directors. Current Board Chair Jim Barrett, who has held the role since the Company’s inception, will not seek re-election as he retires from the Board of Directors and scales back participation in several organizations. Current GlycoMimetics Board Member Tim Pearson will become Board Chair as of the close of the Company’s annual meeting on May 17, 2019.

First Quarter 2019 Financial Results:

Cash position: As of March 31, 2019, GlycoMimetics had cash and cash equivalents of $195.6 million as compared to $209.9 million as of December 31, 2018.

R&D Expenses: The Company’s research and development expenses increased to $11.8 million for the quarter ended March 31, 2019 as compared to $9.0 million for the first quarter of 2018. These increases were primarily the result of the Company’s Phase 3 clinical trial in relapsed or refractory AML patients.

G&A Expenses: The Company’s general and administrative expenses increased to $3.4 million for the quarter ended March 31, 2019 as compared to $2.9 million for the quarter ended March 31, 2018. The increase was due to higher patent, legal and non-cash stock-based compensation expenses.

Shares Outstanding: Shares outstanding as of March 31, 2019 were 43,180,169.

The Company will host a conference call and webcast today at 8:30 a.m. ET. The dial-in number for the conference call is (844) 413-7154 (U.S. and Canada) or (216) 562-0466 (international) and entering passcode 6537429. To access the live audio webcast, or the subsequent archived recording, visit the "Investors – Events & Presentations" section of the GlycoMimetics website at www.glycomimetics.com. The webcast will be recorded and available for replay on the GlycoMimetics website for 30 days following the call.

About Uproleselan (GMI-1271)

Uproleselan (yoo’ pro le’ sel an) is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. In a Phase 1/2 clinical trial, uproleselan was evaluated in both newly diagnosed elderly and relapsed/refractory patients with AML. In both populations, patients treated with uproleselan together with standard chemotherapy achieved better than expected remission rates and overall survival compared to historical controls, which have been derived from results from third party clinical trials evaluating standard chemotherapy, as well as lower than expected induction-related mortality rates. Treatment in these patient populations was generally well tolerated, with fewer than expected adverse effects. The U.S. Food and Drug Administration (FDA) has granted uproleselan Breakthrough Therapy Designation for the treatment of adult AML patients with relapsed/refractory (R/R) disease. GlycoMimetics is progressing a comprehensive development program across the clinical spectrum of AML.

About Rivipansel

Rivipansel, the most advanced drug candidate in the GlycoMimetics pipeline, is a glycomimetic drug candidate that acts as a pan-selectin antagonist, meaning it binds to all three members of the selectin family – E-, P- and L-selectin. The first potential indication for rivipansel is vaso-occlusive crisis (VOC) of sickle cell disease (SCD), one of the most severe complications of SCD which can result in acute ischemic organ injury at one or more sites. By reducing cell adhesion, activation and inflammation that are believed to contribute to reduced blood flow through the microvasculature during VOC, GlycoMimetics believes that rivipansel could be the first drug to interrupt the underlying cause of VOC, thereby potentially enabling patients to leave the hospital more quickly. Pfizer Inc., the exclusive licensee of rivipansel for clinical development and worldwide commercialization, is conducting a Phase 3 clinical trial for rivipansel in SCD.

About GMI-1359

GMI-1359 is designed to simultaneously inhibit both E-selectin and CXCR4. E-selectin and CXCR4 are both adhesion molecules involved in tumor trafficking and metastatic spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound could improve efficacy in the treatment of cancers that involve the bone marrow such as AML and multiple myeloma or in solid tumors that metastasize to the bone, such as prostate cancer and breast cancer. GMI-1359 has completed a Phase 1 clinical trial in healthy volunteers. In the second half of 2019, the Company plans to initiate an exploratory clinical trial in individuals with breast cancer whose tumors have spread to bone.

On May 2, 2019 Geron Corporation (Nasdaq: GERN) reported financial results for the first quarter ended March 31, 2019 (Press release, Geron, MAY 2, 2019, View Source [SID1234535556]). As of the quarter-end, the Company had approximately $170 million in cash and marketable securities, which is sufficient to support the commencement of late-stage development for imetelstat in lower risk myelodysplastic syndromes (MDS).

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 continue to make good progress on our 2019 objectives," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "We are on track to assume sponsorship of the IND for imetelstat by the end of the second quarter, as expected, which will enable us to open enrollment of the planned Phase 3 portion of IMerge by mid-year. In addition, our expanding in-house leadership and drug development team will support the accomplishment of our 2019 objectives and beyond."

First Quarter 2019 Results

For the first quarter of 2019, the Company reported a net loss of $10.1 million, or $0.05 per share, compared to $7.2 million, or $0.04 per share, for the comparable 2018 period.

Revenues for the first quarter of 2019 were $57,000 compared to $318,000 for the comparable 2018 period. Revenues for 2019 and 2018 included royalty and license fee revenues under various non-imetelstat license agreements. The decrease in revenues for the three months ended March 31, 2019 compared to the same period in 2018 primarily reflects a reduction in the number of active license agreements as a result of patent expirations on the underlying technology.

Total operating expenses for the first quarter of 2019 were $11.4 million compared to $7.8 million for the comparable 2018 period.

Research and development expenses for the first quarter of 2019 were $5.9 million compared to $2.4 million for the comparable 2018 period. The increase in research and development expenses for first quarter of 2019 compared to the same period in 2018 primarily reflects higher imetelstat development costs under the former collaboration agreement with Janssen Biotech, Inc. (Janssen) due to Geron’s payment responsibility increasing from 50% to 100% following the termination of the collaboration agreement; new costs for the imetelstat program transition from Janssen to Geron, including for consultants and the Company’s contract research organization (CRO); and increased expenses related to additional development headcount.

General and administrative expenses for the first quarter of 2019 were $5.5 million compared to $5.3 million for the comparable 2018 period. The increase in general and administrative expenses in the first quarter of 2019 compared to same period in 2018 primarily reflects recruitment expenses for new members for the Company’s board of directors.

Interest and other income for the first quarter of 2019 was $1.2 million compared to $394,000 for the comparable 2018 period. The increase in interest and other income for 2019 compared to 2018 primarily reflects higher yields on the Company’s marketable securities portfolio.

Conference Call for Imetelstat Program Update

In lieu of a first quarter conference call, Geron will host a conference call to provide an imetelstat program update at 9:00 a.m. ET on Thursday, May 16, 2019.

Participants may access the conference call live via telephone by dialing domestically +1 (877) 303-9139 or internationally +1 (760) 536-5195. The conference ID is 1264477. A live, listen-only webcast will also be available on the Company’s website at www.geron.com/investors/events. If you are unable to listen to the live call, an archived webcast will be available on the Company’s website for 30 days.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the suppression of malignant progenitor cell clone proliferation, which allows potential recovery of normal hematopoiesis. Ongoing clinical studies of imetelstat include a Phase 2/3 trial called IMerge in lower risk myelodysplastic syndromes (MDS) and a Phase 2 trial called IMbark in Intermediate-2 or High-risk myelofibrosis. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for the treatment of patients with transfusion-dependent anemia due to lower risk MDS who are non-del(5q) and refractory or resistant to an erythroid stimulating agent.

On May 2, 2019 Pacira BioSciences, Inc. (Nasdaq: PCRX) reported financial results for the first quarter of 2019 (Press release, Pacira Pharmaceuticals, MAY 2, 2019, View Source;p=RssLanding&cat=news&id=2396834 [SID1234535554]).

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!

"During the quarter, Pacira achieved significant sales growth while executing several key strategic initiatives, contributing to strong momentum we expect to continue for the rest of 2019," said Dave Stack, chairman and chief executive officer of Pacira BioSciences. "We continue to drive our focused strategy and expect to deliver another year of record EXPAREL sales. We are seeing accelerated penetration in soft tissue procedures, driven by the strong and growing body of evidence around regional pain management approaches that utilize field blocks and nerve blocks as the core of a multimodal non-opioid strategy. In addition, our significant partnership with Johnson & Johnson in orthopedic procedures continues to solidify the role of EXPAREL as the foundation of non-opioid solutions for rotator cuff, spine, joint reconstruction, and hip fracture procedures. Our active customer base is steadily expanding with ambulatory and oral surgery centers both remaining key drivers of new EXPAREL patients."

Mr. Stack continued: "Finally, through our recent MyoScience acquisition, we were pleased to add the iovera° system to our non-opioid franchise as we broaden our strategic reach in this critical area of pain management."

First Quarter 2019 Financial Results

Total revenues were $91.3 million in the first quarter of 2019, a 22.4 percent increase over the $74.6 million reported for the first quarter of 2018.

EXPAREL net product sales were $90.6 million in the first quarter of 2019, a 22.4 percent increase over the $74.0 million reported for the first quarter of 2018 with one less selling day in the first quarter of 2019.

Total operating expenses were $90.2 million in the first quarter of 2019, compared to $81.5 million in the first quarter of 2018.

GAAP net loss was $2.8 million, or $0.07 per diluted share, in the first quarter of 2019, compared to a GAAP net loss of $10.7 million, or $0.26 per diluted share, in the first quarter of 2018.

Non-GAAP net income of $9.3 million, or $0.22 per diluted share, in the first quarter of 2019, compared to non-GAAP net income of $0.9 million, or $0.02 per diluted share, in the first quarter of 2018.

Cash provided by operations was $3.5 million in the first quarter of 2019, compared to cash used in operations of $2.7 million in the first quarter of 2018. Pacira ended the first quarter of 2019 with cash, cash equivalents and short-term investments ("cash") of $412.4 million. On April 9, 2019, we completed our acquisition of MyoScience for $120.0 million in cash.
Recent and Upcoming Business Highlights

MyoScience acquisition advances leadership in non-opioid pain management with FDA-approved iovera° system. In April 2019, Pacira completed its acquisition of MyoScience, Inc., a privately held medical technology company, adding the innovative iovera° system to the Pacira commercial offering. The iovera° system is a novel, non-opioid treatment that alleviates pain through a cryoanalgesia mechanism, which applies intensely focused cold therapy to a specific nerve to interrupt its ability to transmit a pain signal. Upon completion of the acquisition, Pacira changed its corporate name to Pacira BioSciences, Inc.
Results from Phase 4 study of EXPAREL in patients undergoing Cesarean section accepted for oral presentation at Society for Obstetric Anesthesia and Perinatology Annual Meeting. The podium presentation, entitled "Liposomal Bupivacaine Transversus Abdominis Plane Block for Pain after Cesarean Delivery: Results from a Multicenter, Randomized, Double-Blind, Controlled Trial" will be delivered on May 4 in Phoenix, Arizona.
New study of EXPAREL for third molar extractions shows significantly reduced opioid use; data accepted for presentation at International Association of Dental Research Meeting. The poster presentation, "Postsurgical Pain Management after Third-Molar Extraction" will be delivered on June 20, 2019 in Vancouver, BC, Canada.
New analysis shows enhanced recovery pathway that includes EXPAREL facilitates rapid discharge, high satisfaction and limited opioid use in Medicare patients undergoing total joint replacement. In March 2019, Pacira announced new data showing that a patient-optimizing, opioid-sparing enhanced recovery after surgery pathway that includes intraoperative infiltration with EXPAREL results in high rates of early discharge and patient satisfaction among Medicare-insured patients undergoing total knee or hip arthroplasty. Findings also demonstrate that the vast majority of patients do not require more than a 7-day opioid prescription following discharge.
2019 Financial Guidance

Pacira updated its 2019 financial guidance to include net product sales of iovera° (from the April 9, 2019 acquisition date onward) and reiterated all remaining 2019 financial guidance as follows:

EXPAREL net product sales of $400 million to $410 million.

iovera° net product sales of $8 million to $10 million.

Non-GAAP gross margins of 75% to 76%.

Non-GAAP research and development (R&D) expense of $60 million to $70 million.

Non-GAAP selling, general and administrative (SG&A) expense of $165 million to $175 million.

Stock-based compensation of $30 million to $35 million.
See "Non-GAAP Financial Information" and "Reconciliations of GAAP to Non-GAAP 2019 Financial Guidance" below.