On August 7, 2018 Array BioPharma Inc. (NASDAQ: ARRY) reported it has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for encorafenib (BRAFTOVI), in combination with binimetinib (MEKTOVI) and cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC) as detected by an FDA-approved test, after failure of one to two prior lines of therapy for metastatic disease (Press release, Array BioPharma, AUG 7, 2018, View Source [SID1234528516]). BRAFV600E-mutant mCRC patients have a mortality risk more than double that of mCRC patients without the mutation, and currently there are no therapies specifically approved for this high unmet need population. [1-6]

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Breakthrough Therapy Designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition where preliminary clinical evidence indicates that they may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

"We are delighted that the FDA has recognized the potential of this combination for patients with BRAFV600E-mutant metastatic colorectal cancer," said Victor Sandor, M.D., Chief Medical Officer. "As there are no regimens approved specifically for BRAFV600E-mutant mCRC, this designation provides us with the opportunity to work closely with the FDA to potentially accelerate our effort to bring an important treatment option to these patients in critical need."

As presented at the ESMO (Free ESMO Whitepaper) 20thWorld Congress on Gastrointestinal Cancer in June 2018, the results from the safety lead-in of the ongoing randomized Phase 3 BEACON CRC trial showed that, at the time of analysis, the overall survival (OS) data were fully mature through 12.6 months and that the median OS had not yet been reached.

One-year overall survival rate for this cohort was 62%.
Median progression-free survival (mPFS) for patients treated with the triplet was 8 months [95% CI 5.6-9.3] and is similar between patients receiving one prior line of therapy and patients receiving two prior lines of therapy.
Confirmed overall response rate (ORR) was 48% and among the 17 patients who received only one prior line of therapy the ORR was 62%.
The triplet combination was generally well-tolerated with no unexpected toxicities. The most common grade 3 or 4 adverse events seen in at least 10% of patients were fatigue (13%), anemia (10%), increased blood creatine kinase (10%) and increased aspartate aminotransferase (10%).
The triplet combination of BRAFTOVI, MEKTOVI and cetuximab for the treatment of patients with BRAFV600E-mutant metastatic colorectal cancer is investigational and not approved by the FDA.

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer. [7] In the U.S. alone, an estimated 140,250 patients will be diagnosed with cancer of the colon or rectum in 2018, and approximately 50,000 are estimated to die of their disease. [8] In the U.S., BRAF mutations are estimated to occur in 10% to 15% of patients with colorectal cancer and represent a poor prognosis for these patients. [5,6,9,10] The risk of mortality in CRC patients with the BRAFV600E mutation is more than two times higher than for those with wild-type BRAF. [11] Several irinotecan plus cetuximab-containing regimens, similar to the BEACON CRC control arm, have established clinical activity benchmarks in BRAFV600E-mutant mCRC patients, whose disease has progressed after one or two prior lines of therapy, between 4% to 8% ORR, 1.8 and 2.5 months mPFS and 4 and 6 months mOS. [1-6,12]

About BEACON CRC
BEACON CRC is a randomized, open-label, global trial evaluating the efficacy and safety of BRAFTOVI, MEKTOVI and cetuximab in patients with BRAFV600E-mutant mCRC whose disease has progressed after one or two prior regimens. BEACON CRC is the first and only Phase 3 trial designed to test a BRAF/MEK combo targeted therapy in BRAFV600E-mutant mCRC. Thirty patients were treated in the safety lead-in and received the triplet combination (BRAFTOVI 300 mg daily, MEKTOVI 45 mg twice daily and cetuximab per label). Of the 30 patients, 29 had a BRAFV600E mutation. MSI-H, resulting from defective DNA mismatch repair, was detected in only 1 patient. As previously announced, the triplet combination demonstrated good tolerability, supporting initiation of the randomized portion of the trial.

The randomized portion of the BEACON CRC trial is designed to assess the efficacy of BRAFTOVI in combination with cetuximab with or without MEKTOVI compared to cetuximab and irinotecan-based therapy. Approximately 615 patients are expected to be randomized 1:1:1 to receive triplet combination, doublet combination (BRAFTOVI and cetuximab) or the control arm (irinotecan-based therapy and cetuximab). The primary endpoint of the trial is overall survival of the triplet combination compared to the control arm. Secondary endpoints address efficacy of the doublet combination compared to the control arm, and the triplet combination compared to the doublet therapy. Other secondary endpoints include PFS, ORR, duration of response, safety and tolerability. Health related quality of life data will also be assessed. The trial is being conducted at over 200 investigational sites in North America, South America, Europe and the Asia Pacific region. Patient enrollment is expected to be completed around the end of 2018.

About BRAFTOVI + MEKTOVI
BRAFTOVI (encorafenib) is an oral small molecule BRAF kinase inhibitor and MEKTOVI (binimetinib) is an oral small molecule MEK inhibitor which target key enzymes in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma, colorectal cancer, non-small cell lung cancer, thyroid and others. In the U.S., BRAFTOVI + MEKTOVI are approved for the treatment of unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma.

Array has exclusive rights to BRAFTOVI and MEKTOVI in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea, Medison exclusive rights to commercialize both products in Israel and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America.

BRAFTOVI and MEKTOVI are not approved outside of the United States. The European Medicines Agency (EMA), the Swiss Medicines Agency (Swissmedic) and the Australian Therapeutic Goods Administration (TGA) are currently reviewing the Marketing Authorization Applications, and the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan is currently reviewing the Manufacturing and Marketing Approval Applications for BRAFTOVI and MEKTOVI.

Indications and Usage
BRAFTOVI (encorafenib) and MEKTOVI (binimetinib) are kinase inhibitors indicated for use in combination for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test.

Limitations of Use: BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma.

BRAFTOVI + MEKTOVI Important Safety Information
The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted.

Warnings and Precautions
New Primary Malignancies: New primary malignancies, cutaneous and non-cutaneous malignancies can occur. In the COLUMBUS trial, cutaneous squamous cell carcinoma, including keratoacanthoma, occurred in 2.6% and basal cell carcinoma occurred in 1.6% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies.

Tumor Promotion in BRAF Wild-Type Tumors: Confirm evidence of BRAFV600E or BRAFV600Kmutation prior to initiating BRAFTOVI.

Cardiomyopathy: In the COLUMBUS trial, cardiomyopathy occurred in 7% and Grade 3 left ventricular dysfunction occurred in 1.6% of patients. Cardiomyopathy resolved in 87% of patients. Assess left ventricular ejection fraction by echocardiogram or MUGA scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal.

Venous Thromboembolism (VTE): In the COLUMBUS trial, VTE occurred in 6% of patients, including 3.1% of patients who developed pulmonary embolism.

Hemorrhage: In the COLUMBUS trial, hemorrhage occurred in 19% of patients and ≥Grade 3 hemorrhage occurred in 3.2% of patients. Fatal intracranial hemorrhage in the setting of new or progressive brain metastases occurred in 1.6% of patients.

Ocular Toxicities: In the COLUMBUS trial, serous retinopathy occurred in 20% of patients; 8% were retinal detachment and 6% were macular edema. Symptomatic serous retinopathy occurred in 8% of patients with no cases of blindness. In patients with BRAF mutation-positive melanoma across multiple clinical trials, 0.1% of patients experienced retinal vein occlusion (RVO). Permanently discontinue MEKTOVI in patients with documented RVO. In COLUMBUS, uveitis, including iritis and iridocyclitis, was reported in 4% of patients. Assess for visual symptoms at each visit. Perform ophthalmic evaluation at regular intervals and for any visual disturbances.

Interstitial Lung Disease (ILD): ILD, including pneumonitis, occurred in 0.3% of patients with BRAFmutation-positive melanoma across multiple clinical trials. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD.

Hepatotoxicity: In the COLUMBUS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 6% for alanine aminotransferase (ALT) and 2.6% for aspartate aminotransferase (AST). Monitor liver laboratory tests before and during treatment and as clinically indicated.

Rhabdomyolysis: In the COLUMBUS trial, elevation of laboratory values of serum creatine phosphokinase (CPK) occurred in 58% of patients. Rhabdomyolysis was reported in 0.1% of patients with BRAF mutation-positive melanoma across multiple clinical trials. Monitor CPK periodically and as clinically indicated.

QTc Prolongation: In the COLUMBUS trial, an increase in QTcF to >500 ms was measured in 0.5% (1/192) of patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms.

Embryo-Fetal Toxicity: BRAFTOVI or MEKTOVI can cause fetal harm when administered to pregnant women. Nonhormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI + MEKTOVI.

Adverse Reactions
The most common adverse reactions (≥20%, all Grades, in the COLUMBUS trial) were: fatigue, nausea, diarrhea, vomiting, abdominal pain, arthralgia, myopathy, hyperkeratosis, rash, headache, constipation, visual impairment, serous retinopathy.

In the COLUMBUS trial, the most common laboratory abnormalities (≥20%, all Grades) included: increased creatinine, increased CPK, increased gamma glutamyl transferase, anemia, increased ALT, hyperglycemia, increased AST, and increased alkaline phosphatase.

Drug interactions
Avoid concomitant use of strong or moderate CYP3A4 inhibitors or inducers and sensitive CYP3A4 substrates with BRAFTOVI. Modify BRAFTOVI dose if concomitant use of strong or moderate CYP3A4 inhibitors cannot be avoided.

Please see full Prescribing Information for BRAFTOVI and full Prescribing Information for MEKTOVI for additional information. You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Array at 1-844-Rx-Array (1-844-792-7729).

On August 7, 2018 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported financial results for the three months ended June 30, 2018 and reported on corporate developments. Unless specified otherwise, all amounts are in US dollars (Press release, Aptose Biosciences, AUG 7, 2018, View Source;p=RssLanding&cat=news&id=2362628 [SID1234528649]).

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Total cash and cash equivalents and investments as of June 30, 2018 were $18.5 million which, based on current operations, provide the Company with sufficient resources to fund research and development and operations into 2H 2019. Since January 1, 2018, Aptose has raised $15.0 million from the Common Shares Purchase Agreement with Aspire Capital, and $5.2 million from the ATM with Cantor Fitzgerald.

During the quarter, payment of one-time license fees totaling $5.0 million were made to CrystalGenomics, Inc. ("CG") for full execution of the CG-806 license agreement and to capture rights to the China region. Consequently, the net loss for the quarter ended June 30, 2018 was $10.3 million ($0.30 per share) compared with $2.4 million ($0.11 per share) in the quarter ended June 30, 2017, and total cash used in operating activities was $9.3 million compared with $2.6 million in the quarter ended June 30, 2017. Excluding the one-time license fees payments, net loss would have been $5.3 million and $0.16 per share.

"During the second quarter, important advancements were achieved with both of our hematology product candidates, APTO-253 and CG-806. Most notably, our diligence to effectively address the past formulation and manufacturing setbacks with APTO-253 was rewarded with lifting of the clinical hold," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We now are eager to return to the clinic with this exciting molecule that inhibits expression of the MYC oncogene, which is operative in many hematologic cancers, particularly AML. Separately during the quarter, our CG-806 pan-FLT3/pan-BTK inhibitor was shown to exert potent and broad range killing of malignant cells collected from the bone marrow of patients with hematologic malignancies, and IND-enabling GLP toxicology studies were initiated. Subsequent to the end of the quarter, the in-life portions of the IND-enabling studies were completed. We now are focused on initiating clinical trials and are on track to submit an IND for CG-806 before year-end."

Corporate Highlights

FDA lifts clinical hold so MYC Inhibitor APTO-253 can return to Phase 1b trial – In June, the U.S. Food and Drug Administration (FDA) lifted the clinical hold on APTO-253 following the company’s actions to address chemistry, formulation and manufacturing setbacks in the past. APTO-253, Aptose’s investigational drug for hematologic cancers, is the only known clinical-stage molecule that has the potential to directly target and inhibit expression of the MYC oncogene shown to be a causative factor in many malignancies, including acute myeloid leukemia (AML).

Preclinical data presentations on APTO-253 and CG-806 support clinical development – In addition to the preclinical data on APTO-253 and CG-806 that were presented at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference held in April and previously discussed, Aptose presented preclinical data demonstrating that CG-806 directly kills a broader range of patient-derived hematologic cancer cells with greater potency than ibrutinib, a BTK inhibitor approved for the treatment of certain hematologic malignancies. The data were presented in a poster at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June. Aptose also announced the publication of two separate articles in the June 2018 issue of Molecular Cancer Therapeutics, a peer-reviewed journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). These data provide new insights into the mechanism of action of APTO-253 and how this novel agent inhibits expression of the MYC gene, an oncogene that promotes tumor growth and resistance to drugs in AML and other cancers.

CG-806 pre-IND progress – Aptose successfully manufactured GLP-grade CG-806 drug substance and formulated drug product, performed animal dose range finding preclinical studies, initiated IND-enabling GLP animal toxicology and pharmacokinetic studies, and then completed the in-life dosing portion of those toxicology studies subsequent to the end of the quarter. The Company also completed manufacture of a GMP-grade batch of CG-806 planned for use in human clinical trials.

CG-806 license now includes all territories outside of Korea – In May, Aptose exercised its option under the 2016 Option Agreement to exclusively license CG-806 from CrystalGenomics, providing Aptose global rights to develop and commercialize CG-806 for all indications outside of Korea and China – the Licensed Territory. The exercise triggered a payment of $2.0 million to CrystalGenomics, and CrystalGenomics is eligible for regulatory and sales milestone payments, as well as royalties on product sales in the Licensed Territory. In June, Aptose entered into a separate license agreement with CrystalGenomics, Inc., providing Aptose with the China rights to CG-806 (including People’s Republic of China, Hong Kong and Macau). Aptose made an upfront payment of $3.0 million and CrystalGenomics is eligible for development, regulatory and commercial-based milestones, as well as single-digit royalties on product sales specifically in China.

New share purchase agreement with Aspire Capital – As previously announced in May, Aptose entered into a Common Share Purchase Agreement of up to $20 Million with Aspire Capital Fund, LLC ("Aspire Capital"). Under the terms of the Agreement, Aspire Capital has committed to purchase up to $20 million of common shares of Aptose, at Aptose’s request from time to time until April 7, 2020.
Financial Results

The increase in the net loss during the three months ended June 30, 2018 compared with the three months ended June 30, 2017 results was primarily driven by the payment of one-time license fees in the amount $5.0 million to CrystalGenomics ("CG") for full execution of the license agreement and to capture worldwide rights (excluding Korea), from higher research and development expenses related to our CG-806 and APTO-253 programs, and from higher professional fees related to regulatory filings in support of financing activities. Excluding the one-time license fees payments, net loss for the three months ended June 30, 2018 would have been $5.3 million and $0.16 per share.

The increase in the net loss during the six months ended June 30, 2018 compared with the six months ended June 30, 2017 results mostly from $5.0 million in license fees paid to CG for worldwide rights (excluding Korea), higher research and development expenses related to our CG-806 and APTO-253 programs higher professional fees related to regulatory filings in support of financing activities and from $2.7 million in non-cash expenses related to stock option compensation. Excluding the one-time license fees payments, net loss for the six months ended June 30, 2018 would have been $12.1 million and $0.39 per share.

Research and Development
Components of research and development expenses

The changes in research and development expenses in the three and six months ended June 30, 2018 as compared to the three and six months ended June 30, 2017 result from the following:

License fees paid to CrystalGenomics of $2.0 million for development and commercial rights of CG-806 in all territories outside of Korea and China, and a further $3.0 million paid for development and commercial rights of CG-806 in China (including People’s Republic of China, Hong Kong and Macau). CrystalGenomics is eligible for development, regulatory and commercial-based milestones as well as royalties on future product sales.
An increase in research and development activities related to our CG-806 development program. In the period ended March 31, 2018, we completed the manufacture of a batch of the drug substance to be used in Dose Range Finding (DRF) toxicity studies and then complete the dose range finding studies in two species. In the three-month period ended June 30, 2018, we manufactured a GLP batch of CG-806 to be used in toxicity studies, completed the manufacture of a GMP batch of the drug substance for future clinical trials, initiated the IND-enabling GLP toxicology and pharmacokinetic studies in two species, and then completed the in-life dosing portion of those IND-enabling studies subsequent to the end of the quarter. In the comparative periods, activities related to our CG-806 program included mostly formulation and PK studies.
An increase in expenditures on the APTO-253 program. In the period ended March 31, 2018, we completed production of a GMP batch of drug product, and we initiated necessary studies to present to the FDA. In the three-month period ended June 30, 2018, we completed the required studies for the FDA, we initiated the manufacturing of an additional clinical batch of APTO-253 and we increased clinical activities in preparation to return APTO-253 to the clinic. In the comparative periods, we were conducting root cause analysis to determine the cause of a manufacturing issue that had resulted in the program being on clinical hold.
An increase in salaries expense mostly related to additional clinical research staff hired at the end of the prior fiscal year to prepare for returning APTO-253 to the clinic.
An increase in stock option compensation related mostly to stock options granted in the three months ended March 31, 2018, of which 100,000 with a grant date fair value of $2.03 which vested immediately.
General and Administrative
Components of general and administrative expenses

General and administrative expenses excluding salaries increased in the three and six months ended June 30, 2018, compared with the three and six months ended June 30, 2017. The increase is mostly the result of higher professional fees related to regulatory filings for the base shelf prospectus and two follow-on supplemental prospectus filings, higher investor relations, higher patent fees associated with our expanded IP portfolio, and higher office administrative costs associated with having additional employees.

In the three-month period ended June 30, 2018, we issued 170,261 shares to Aspire Capital as a commitment fee for entering into a $20 Million share purchase agreement. We recorded $600 thousand in general and administrative expenses related to the issuance of these shares.

Salaries expenses in the three months ended June 30, 2018, increased in comparison with the three months ended June 30, 2017, due mostly to additional headcount to support the increased activities and to salary increases. Salary expenses in the six months ended June 30, 2018, decreased in comparison with the six months ended June 30, 2017, due mostly to separation payments made in the period ended March 31, 2017, offset by higher salaries in the current period.

Stock-based compensation increased in the six months ended June 30, 2018, compared with the six months ended June 30, 2017 mostly related to stock options granted in the three-month period ended March 31, 2018, of which 750,000 with a grant date fair value of $2.03 vested immediately, and also as a result of large forfeitures in the three months ended March 31, 2017.

Conference Call and Webcast

Aptose will host a conference call today, Tuesday, August 7, 2018 at 5:00 p.m. EDT to discuss results for the three and six months ended June 30, 2018. Participants can access the conference call by dialing (844) 882-7834 (North American toll-free number) and (574) 990-9707 (International) and using conference ID #2693419. The conference call webcast can be accessed here and will also be available through a link on the Investor Relations section of Aptose’s website at ir.aptose.com. An archived version of the webcast along with a transcript will be available on the Company’s website for 30 days. An audio replay of the webcast will be available approximately two hours after the conclusion of the call through August 14, 2018 by dialing (855) 859-2056, using the conference ID # 2693419.

The live conference call can also be accessed through a link on the Investor Relations section of Aptose’s website at ir.aptose.com. Please log onto the webcast at least 10 minutes prior to the start of the call to ensure time for any software downloads that may be required. An archived version of the webcast along with a transcript will be available on the company’s website for 30 days.

On August 7, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported financial results for the second quarter ended June 30, 2018, and provided an update on recent developments (Press release, Bellicum Pharmaceuticals, AUG 7, 2018, View Source [SID1234528497]).

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"We made substantial progress during the second quarter, with key data readouts expected later in 2018," said Bellicum’s President & CEO Rick Fair. "Registration studies with our polyclonal allogeneic cell therapy, BPX-501, are on track and we expect to file MAAs in the European Union in 2019. In anticipation of these filings, we have begun to staff a European organization and initiate pre-launch activities. In addition, based on the encouraging results to date in pediatric leukemias, we are advancing plans to expand the BPX-501 opportunity with a late-stage trial in adult AML patients."

Continued Mr. Fair: "The Phase 1 study of our lead GoCAR-T program, BPX-601, continues to enroll and we plan to report initial results before the end of 2018. We are also hard at work preparing IND/IMPD regulatory submissions for two new dual-switch GoCAR-T programs we expect to enter the clinic in 2019."

PROGRAM HIGHLIGHTS AND CURRENT UPDATES

Registration Studies on Track in Europe with BPX-501
Prospective enrollment was completed in the BP-004 and C-004 pediatric trials in patients with leukemias, lymphomas, and inherited blood disorders. These trials will serve as the basis for the planned 2019 European MAA regulatory filings. During the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June, Bellicum reported compelling interim data from BP-004:

Additional interim results from both the BP-004 and the C-004 clinical trials will be presented at a medical conference later this year, with final results expected in early 2019. Bellicum also continues to advance its plans to initiate a late-stage trial of BPX-501 in adult AML patients by the end of the year.

Commercial Planning Activities Underway in Europe for BPX-501
Bellicum named Thierry Darcis, M.D., M.B.A., as General Manager of Europe to lead commercialization plans for BPX-501. Dr. Darcis has extensive experience launching orphan products in Europe and has led commercial teams that supported successful product introductions for ViroPharma and NPS Pharmaceuticals. He also held leadership roles with Zogenix, Novartis Vaccines and GlaxoSmithKline.

BPX-601 and BPX-701 Trials Advancing
BPX-601 is Bellicum’s first GoCAR-T product candidate and is the first controllable CAR-T cell to enter clinical trials. The Company expects to report preliminary findings from the Phase 1 dose-escalation safety study of BPX-601 in adults with nonresectable pancreatic cancer who test positive for prostate stem cell antigen (PSCA) later this year, and is currently implementing an amendment to expand the study to gastric and prostate cancer patients. A Phase 1 study of BPX-701 continues to screen patients, and additional clinical sites are being added to the trial to accelerate enrollment.

Second Quarter 2018 Financial Results

Bellicum reported a net loss of $24.2 million for the second quarter of 2018 and $47.0 million for the six months ended June 30, 2018, respectively, compared to a net loss of $24.5 million and $46.4 million for the comparable periods of 2017. The results included non-cash, share-based compensation charges of $3.6 million and $7.2 million for the second quarter and six months ended June 30, 2018, and $3.2 million and $6.6 million for the comparable periods in 2017.

As of June 30, 2018, cash, restricted cash and investments totaled $135.3 million. Based on current operating plans, Bellicum continues to expect that current cash resources will be sufficient to meet operating requirements through 2019.

Research and development expenses were $18.4 million and $34.9 million, for the three and six months ended June 30, 2018, respectively, compared to $18.0 million and $33.3 million during the comparable periods in 2017.

General and administrative expenses were $5.4 million and $11.1 million for the three and six months ended June 30, 2018, respectively, compared to $5.5 million and $11.4 million during the comparable periods in 2017.

At June 30, 2018, Bellicum had 43,346,220 shares of common stock outstanding.

Conference Call and Webcast
Bellicum management will host a webcast and conference call at 5:00 p.m. Eastern today to discuss the financial results and provide a corporate update. To access the call, participants should dial 877-407-3103 (domestic) and 201-493-6791 (international) at least 10 minutes prior to the start of the call. The event will be webcast live and can also be accessed in the Investors & Media section of bellicum.com. An archived version of the webcast will also be available for replay in the Investors & Media section of the Bellicum website for at least two weeks following the call.

About BPX-501
BPX-501 is an adjunct T cell therapy administered after allogeneic HSCT, comprising genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD or other T-cell mediated transplant complications occur. This may enable physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections, and enhance graft-versus-leukemic activity while minimizing GvHD side effects.

About BPX-601
BPX-601 is a GoCAR-T product candidate containing Bellicum’s proprietary inducible MyD88/CD40, or iMC, activation switch, designed to treat solid tumors expressing prostate stem cell antigen, or PSCA. Preclinical data show enhanced T cell proliferation, persistence and in vivo anti-tumor activity compared to traditional CAR-T therapies. In addition to pancreatic cancer, PSCA is expressed in several other solid tumor indications, including gastric and prostate cancers.

About BPX-701
BPX-701 is a high affinity T cell receptor product candidate designed with the CaspaCIDe safety switch. In preclinical studies, PRAME-specific clones showed high reactivity against a panel of PRAME positive tumor cell lines, metastatic melanoma, sarcomas and neuroblastoma tissues. In vitro study data showed that BPX-701 demonstrated strong affinity to panels of cancer cells presenting PRAME peptides and low affinity to non-tumor cells, as well as elimination of BPX-701 cells in response to rimiducid.

On August 7, 2018 Eagle Pharmaceuticals, Inc. ("Eagle" or "the Company") (Nasdaq:EGRX) reported its financial results for the three and six months ended June 30, 2018 (Press release, Eagle Pharmaceuticals, AUG 7, 2018, View Source [SID1234528517]). Highlights of and subsequent to the second quarter of 2018 include:

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Business and Recent Highlights:

EHS clinical trial for RYANODEX will be conducted August 20 – 24, 2018 during the Hajj pilgrimage;
Eagle received a favorable decision by the U.S. District Court for the District of Columbia granting seven years of orphan drug exclusivity (ODE) in the U.S., for BENDEKA (bendamustine hydrochloride injection, or bendamustine HCI) until December 2022 and denying the Food and Drug Administration’s (FDA’s) attempt to preemptively exclude TREANDA generics from the scope of exclusivity;
Data from the fulvestrant clinical trial expected in the fourth quarter of 2018;
Advancing discussions with U.S. military to formalize clinical and regulatory plans for RYANODEX in the treatment of nerve agent exposure;
United States Patent and Trademark Office issued patent number 10,010,533 for BENDEKA. The USPTO has now issued or allowed a total of 15 U.S. patents in the BENDEKA family of patents expiring from 2021 to 2033;
Eagle was first to file a vasopressin 1ml injection ANDA, which was accepted for filing by the FDA in April; and
A second source manufacturing facility for Eagle’s bendamustine products has been approved by the FDA.
Financial Highlights:

Second quarter 2018

Total revenue for the second quarter of 2018 was $59.3 million, compared to $50.1 million in the second quarter of 2017;
Eagle launched bendamustine hydrochloride 500ml solution ("Big Bag") on May 15, 2018 and Big Bag product sales were $8.1 million in the second quarter of 2018;
Q2 2018 Ryanodex product sales were $7.2 million, up 38% compared to Q2 2017;
Q2 2018 net income was $2.7 million, or $0.18 per basic and $0.17 per diluted share, compared to net income of $4.5 million, or $0.30 per basic and $0.28 per diluted share in Q2 2017;
Q2 2018 Adjusted Non-GAAP net income was $14.7 million, or $0.99 per basic and $0.95 per diluted share, compared to Adjusted Non-GAAP net income of $7.9 million, or $0.52 per basic and $0.49 per diluted share in Q2 2017;
During Q2 2018, Eagle purchased an additional $3.5 million of Eagle common stock as part of its share buyback program; since August 2016, Eagle has repurchased $91.3 million of Eagle common stock; and
Cash and cash equivalents were $100.2 million, accounts receivable was $69.4 million, and debt was $47.5 million as of June 30, 2018.
Reiterating 2018 Expense Guidance:
R&D expense is expected to be in the range of $46 – $50 million ($40 – $44 million on a non-GAAP basis)
SG&A expense is expected to be in the range of $61 – $64 million ($44 – $47 million on a non-GAAP basis)
"We believe 2018 will be another solid year of growth for Eagle, with continued near-term value creation, and strong upside potential with our advanced pipeline that could meaningfully contribute to the long-term value of the business. This includes protecting the value and longevity of our existing bendamustine franchise where we recently prevailed in litigation and received orphan drug exclusivity until December 2022 for BENDEKA, as well as having recently launched "Big Bag", our 500 mL liquid form bendamustine solution that does not require reconstitution, filling an important need in the market for a lower-cost alternative. Our RYANODEX portfolio is advancing as we take advantage of product and label expansion opportunities for Exertional Heat Stroke and evaluate the neurological impact of nerve agent exposure in collaboration with the U.S. military," stated Scott Tarriff, Chief Executive Officer of Eagle Pharmaceuticals.

"As a result of the favorable court ruling requiring the FDA to grant BENDEKA orphan drug exclusivity, the FDA will not be able to approve any drug applications referencing BENDEKA until the ODE expires in December 2022. The court also denied the FDA’s attempt to preemptively exclude TREANDA generics from the scope of BENDEKA’s ODE. We continue to believe that an appropriate application of ODE would first allow generic TREANDA entrants in December 2022, rather than November 2019 and intend to vigorously pursue our position with the FDA and through additional litigation, if necessary," added Tarriff.

"We look forward to completing our clinical study for RYANODEX for EHS scheduled during the Hajj Pilgrimage, to support the data we have previously collected. We anticipate reporting results for our fulvestrant study later this year, along with progress on other products under development. We look forward to sharing our continued progress to create value for patients and shareholders," concluded Tarriff.

Second Quarter 2018 Financial Results

Total revenue for the three months ended June 30, 2018 was $59.3 million, as compared to $50.1 million for the three months ended June 30, 2017. Royalty revenue was $36.3 million, compared to $37.4 million in the second quarter of 2017. BENDEKA royalties were $34.7 million, compared to $35.1 million in the second quarter of 2017. A summary of total revenue is outlined below:

Gross margin was 69% in the second quarter of 2018, as compared to 72% in the second quarter of 2017. The gross margin on Big Bag was 68%, reflecting royalty obligations to our partners as well as cost of goods sold.

Research and development expenses increased to $15.3 million for the second quarter of 2018, compared to $6.7 million in the second quarter of 2017, largely due to external clinical costs associated with the fulvestrant clinical study. Excluding stock-based compensation and other non-cash and non-recurring items, R&D expense during the second quarter of 2018 was $13.4 million.

SG&A expenses decreased to $16.0 million in the second quarter of 2018 compared to $23.3 million in the second quarter of 2017. The decrease was due to the expiration of the Spectrum co-promotion agreement at the end of June 2017, as well as a reduction in marketing expenses. Excluding stock-based compensation and other non-cash and non-recurring items, second quarter 2018 SG&A expense was $11.7 million.

Net income for the second quarter of 2018 was $2.7 million, or $0.18 per basic and $0.17 per diluted share, compared to net income of $4.5 million, or $0.30 per basic and $0.28 per diluted share in the three months ended June 30, 2017, due to the factors discussed above.

Adjusted Non-GAAP net income for the second quarter of 2018 was $14.7 million, or $0.99 per basic and $0.95 per diluted share, compared to Adjusted Non-GAAP net income of $7.9 million or $0.52 per basic and $0.49 per diluted share in the second quarter of 2017. For a full reconciliation of Adjusted Non-GAAP net income to the most comparable GAAP financial measures, please see the tables at the end of this press release.

Liquidity

As of June 30, 2018, the Company had $100.2 million in cash and cash equivalents and $69.4 million in net accounts receivable, $45.9 million of which was due from Teva Pharmaceutical Industries Ltd. The Company had $47.5 million in outstanding debt.

In the second quarter of 2018, we purchased $3.5 million of Eagle’s common stock as part of our expanded $100 million share buyback program. Since August 2016, we have repurchased $91.3 million of our common stock.

2018 Expense Guidance

2018 R&D expense is expected to be in the range of $46 – $50 million. This reflects expenses for (i) the enrollment of fulvestrant and RYANODEX EHS clinical trials; (ii) API outlays for the fulvestrant and vasopressin programs; and (iii) additional development work on the RYANODEX nerve agent program. Excluding stock-based compensation and other non-cash and non-recurring items, R&D expense is expected to be in the range of $40 – $44 million.

2018 SG&A expense is expected to be in the range of $61 – $64 million. Excluding stock-based compensation and other non-cash and non-recurring items, SG&A expense is expected to be in the range of $44 – $47 million.

Conference Call

As previously announced, Eagle management will host its second quarter 2018 conference call as follows:

Date Tuesday, August 7, 2018
Time 8:30 A.M. EDT
Toll free (U.S.) 877-876-9177
International 785-424-1669
Webcast (live and replay)
www.eagleus.com, under the "Investor + News" section

A replay of the conference call will be available for one week after the call’s completion by dialing 800-727-5306 (US) or 402-220-2670 (International) and entering conference call ID EGRXQ218. The webcast will be archived for 30 days at the aforementioned URL.

On August 7, 2018 Melinta Therapeutics, Inc. (NASDAQ: MLNT), a commercial-stage company discovering, developing and commercializing novel antibiotics to treat serious bacterial infections, reported financial results and provided an update on commercial activities for the quarter ended June 30, 2018 (Press release, Cempra, AUG 7, 2018, View Source [SID1234528650]). Melinta continued to make progress this quarter in its mission to save lives threatened by the global public health crisis of bacterial infections through the development and commercialization of novel antibiotics that provide new therapeutic solutions.

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Q2 2018 and Recent Business Highlights

Completed the hiring of 71 additional field sales personnel bringing total sales representatives to 170

Completed realignment and cross-training of experienced anti-infective sales force across all four products, including Baxdela (delafloxacin), Vabomere (meropenem and vaborbactam), Orbactiv (oritavancin) and Minocin (minocycline) for Injection

Made strong progress on hospital approval process of new launches, Vabomere and Baxdela

Vabomere granted New Technology Add-On Payment (NTAP) by Centers for Medicare & Medicaid Services (CMS), effective Oct. 1, 2018

Continued growth in retail market for Baxdela, driven by specialty retail focus of our sales force

Completed enrollment ahead of schedule for Baxdela Phase III trial for treatment of adults with community acquired bacterial pneumonia ("CABP")

Entered into partnership with CARB-X, receiving up to approximately $6 million to help advance pre-clinical and clinical development of a novel antibiotic class

Launched new antibiotic stewardship program designed to address the growing threat of antimicrobial resistance

Completed follow-on public offering of shares of common stock, raising approximately $115 million in net proceeds

Demonstrated breadth of commercial and clinical programs with 20 presentations at the American Society of Microbiology’s ASM Microbe 2018 meeting

"Melinta took important steps forward during the second quarter, with solid sales performance from our new launches of Baxdela and Vabomere and the completion of a public follow-on offering of common shares that significantly strengthened our long-term financial position," said Dan Wechsler, President and CEO of Melinta. "Product sales remained steady during the quarter and we continued to make excellent progress on our recent launches. We expect our sales trajectory to increase in the second half of the year, powered by our significantly increased presence in the marketplace and our expanded and now fully cross-trained sales force of 170 highly experienced sales representatives, with average hospital expertise of 15 years."

"We also continued to make advancements within our pipeline during the quarter. Our Phase III trial of Baxdela for the treatment of adults with CABP completed enrollment ahead of schedule and is on track for top-line data by the end of 2018. Our discovery organization also continued to advance their important work following the announcement of our agreement with CARB-X that will provide us funding to advance the development of a novel antimicrobial from our ESKAPE pathogen program."

"With the completion of our public offering, we are now in a strong financial position to support our continued growth."

2018 Upcoming Potential Catalysts

Pivotal Phase 3 data for Baxdela in CABP

Vabomere EMA regulatory approval decision

Vabomere Medicare NTAP status effective Oct. 1, 2018

Additional ex-U.S. submissions for Baxdela in Central and South America

Ex-U.S. partnership opportunities for Vabomere, Orbactiv and Minocin for Injection

Additional data and publications at ID Week

IND-enabling studies for the lead ESKAPE compound

Q2 2018 Financial Results

Melinta reported revenue of $12.0 million for the quarter ended June 30, 2018. In addition, the company earned $2.1 million in funding from the Biomedical Advanced Research and Development Authority (BARDA), which it recorded as other income.

During the quarter, as part of the final stages of the integration of the Infectious Disease business acquired from The Medicines Company, Melinta implemented a new, direct-to-wholesaler distribution process that will shorten the Company’s overall supply chain cycle, reduce inventory levels at wholesalers and save fees paid to wholesalers. The change resulted in a one-time negative impact on second quarter revenues of $2.7 million, primarily impacting Orbactiv.

Second quarter of 2018 total net revenue of $12.0 million compares to total net revenue of $4.0 million for the same period in 2017, prior to the acquisition of The Medicines Company ID business and the launch of Baxdela. In the second quarters of 2018 and 2017, we recognized contract research revenue totaling $2.8 million and $4.0 million, respectively. In the second quarter of 2018, net product sales were $9.2 million. The net product sales reflect solid performance of new launches and include the impact described above of the implementation of the new, direct-to-wholesaler distribution process, which occurred during the quarter and resulted in a one-time negative impact of $2.7 million, primarily impacting Orbactiv.

Excludes BARDA grant funding included in Other Income of $2.1 million

Cost of goods sold ("COGS") was $11.0 million for the quarter ended June 30, 2018, of which $6.7 million was comprised of non-cash amortization of intangible assets and the step-up basis in inventory acquired from The Medicines Company in January 2018. Cost of goods sold also included charges of $2.4 million for Baxdela and Vabomere inventory that is approaching shelf life. Adjusted COGS was $2.0 million, excluding these non-cash charges, resulting in an Adjusted Gross Margin of 84% for the second quarter. There were no product sales and therefore no costs of goods sold in the prior year period.

Research and development ("R&D") expenses were $15.8 million for the quarter ended June 30, 2018, compared to $14.1 million for the same period in 2017. The increase was driven by additional headcount and development activities resulting from the acquisition of the infectious disease business from The Medicines Company and the recent merger with Cempra. Adjusted R&D expenses were $15.6 million, which reflects the adjustment for non-cash expenses of $0.2 million.

Selling, general and administrative ("SG&A") expenses were $34.9 million for the quarter ended June 30, 2018, compared to $7.7 million for the same period in 2017. The increase was driven by additional expenses associated with being a larger, public, commercial organization, including the operational impact of both the acquisition of the infectious disease business from The Medicines Company and the Cempra merger, consisting of additional headcount, facilities and commercial infrastructure. Approximately $1.7 million of SG&A expenses were a result of acquisition-related costs and lease exit costs, resulting in Adjusted SG&A expenses of $32.7 million.

Net loss was $55.8 million, or $1.38 per share, for the quarter ended June 30, 2018 compared to a net loss of $20.4 million for the same period in 2017. Net loss per share is impacted by changes in our share count as a result of the Cempra merger and financing related to the acquisition of the infectious disease business from The Medicines Company.

On May 29, 2018, Melinta completed a follow-on public offering of 21.9 million shares of its common stock. The underwriters of the public offering also exercised in full their option to purchase an additional 2.6 million shares of Melinta’s common stock. Net proceeds from the offering were approximately $115.1 million after deducting underwriting discounts and commissions and expenses paid. As of June 30, 2018, Melinta had cash and cash equivalents of $150.1 million.

Q2 2018 and Recent Pipeline and Publication Highlights

20 presentations at ASM Microbe 2018, including pharmacoeconomic analyses of Vabomere and Orbactiv (oritavancin), and analyses showing the rising incidence of Gram-negative pathogens in skin and skin structure infections (SSSIs) and the changes to empiric therapy that may be considered to improve outcomes

12 presentations at the MAD-ID 2018 Annual Meeting, including detailed safety and efficacy findings from the Phase 3 PROCEED studies of Baxdela in patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Findings from the Orbactiv real-world registry demonstrating efficacy and safety consistent with the Phase 3 SOLO program published in Open Forum Infectious Diseases

12 Presentations at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 2018 including six from Vabomere TANGO-2 trial, as well as new in vitro and in vivo findings for Baxdela and a pyrrolocytosine lead molecule

Pyrrolocytosine compound RX-P2382 against ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and Escherichia coli) at ECCMID 2018

TANGO-2 Trial at ECCMID 2018, highlighting outcomes in vulnerable patient populations

Discovery Platform Oral Presentations at ECCMID 2018 and ASM Microbe 2018 Highlighting Progress Towards Leads for Drug-resistant Neisseria gonorrhoeae and Multidrug- and Extremely Drug-resistant ESKAPE Pathogens

Conference Call and Webcast

Melinta’s earnings conference call for the quarter ended June 30, 2018 will be broadcast at 8:30 a.m. ET on August 7, 2018. The live webcast can be accessed under "Events and Presentations" in the Investor Relations section of Melinta’s website at www.melinta.com.

Investors wishing to participate in the call should dial: 877-377-7553 and international investors should dial: 253-237-1151. The conference ID is 9594878. Investors can also access the call at View Source

A live webcast of the call will be available online from the Investor Relations section of the company website at www.melinta.com and will be archived there for 30 days. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 9594878.