On May 7, 2019 MorphoSys AG (FSE: MOR; Prime Standard Segment, MDAX & TecDAX; NASDAQ: MOR) reported results for the first quarter of 2019 (Press release, MorphoSys, MAY 7, 2019, View Source [SID1234535831]).

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"We have made a very good start to the year 2019 with significant achievements in our proprietary and partnered programs as well as in our corporate development," said Dr. Simon Moroney, Chief Executive Officer of MorphoSys AG. "First of all I am very pleased to announce that MOR208 now has been given an International Nonproprietary Name (INN). From now on MOR208 will be called tafasitamab. This marks another major milestone in the development of the compound and together with the strong build-up of our commercial structures and capabilities in the U.S., we get more and more ready for the planned launch in the U.S. mid of next year, given FDA approval. Rolling submission to the FDA continues according to plan, which could support a potential approval in the U.S. in mid-2020. Furthermore, we are encouraged by discussions we have had with European regulatory authorities on a path to market in Europe based on our L-MIND study. A successful outcome here could result in MOR208 (tafasitamab) being on the market in Europe earlier than previously assumed."

"We also saw encouraging progress in other programs. Our partner I-Mab Biopharma initiated pivotal clinical trials of MOR202 in second and third line multiple myeloma during the first quarter. GSK announced its intention to start a phase 3 study of MOR103/GSK3196165 in rheumatoid arthritis later this year. Also, the clinical development of Janssen’s Tremfya(R), the most important program in our Partnered Discovery segment, was further expanded into ulcerative colitis and familial adenomatous polyposis," Dr. Moroney continued.

"With our solid financial position, MorphoSys is well equipped to execute the plans for our proprietary product development. We are excited to have David Trexler join as president and head of our U.S. based subsidiary. He is building our commercial capabilities for a potential launch of MOR208 (tafasitamab) in the U.S., subject, of course, to FDA approval. The increasing royalty stream from Tremfya(R) product sales will continue to provide strong financial support to our plans to become a fully-fledged biopharmaceutical company," said Jens Holstein, Chief Financial Officer of MorphoSys AG.

Financial Review for Q1 2019 (IFRS)

In Q1 2019, MorphoSys continued to focus on applying its proprietary technology and expertise to the research and development of innovative drug candidates, both for partners and for its own account. Group revenues rose to EUR 13.5 million, compared to EUR 2.8 million in the first quarter of 2018. Revenues for the first quarter of 2019 include EUR 11.0 million for success-based payments received primarily from Janssen and I-Mab (Q1 2018: EUR 1.8 million) including an estimate of royalties on net sales of Tremfya(R) amounting to EUR 6.6 million (royalty report from Janssen for Q1 2019 has not yet been received).

In its Proprietary Development segment, MorphoSys focuses on the research and clinical development of its own drug candidates. In Q1 2019, this segment recorded revenues of EUR 5.8 million (Q1 2018: EUR 0.2 million). The increase was primarily driven by a milestone payment of USD 5.0 million from our partner I-Mab due to the start of the pivotal phase 2 development of MOR202 in Taiwan.

In the Partnered Discovery segment, MorphoSys applies its proprietary technology to the discovery of new drug candidates for pharmaceutical companies, benefiting through R&D funding, licensing fees, success-based milestone payments and royalties. Revenues in the Partnered Discovery segment increased from EUR 2.6 million in Q1 2018 to EUR 7.8 million in Q1 2019.

Total operating expenses reached EUR 37.3 million in the first quarter of 2019 compared to EUR 21.9 million in Q1 2018. The increase is mainly driven by higher R&D, selling and general & administrative expenses and the introduction of cost of sales as new item compared to Q1 2018. In Q1 2019, research and development expenses amounted to EUR 24.7 million, as compared to EUR 17.2 million in the first quarter of 2018. Expenses for proprietary R&D, including technology development amounted to EUR 22.6 million in Q1 2019, compared to EUR 15.5 million in the first quarter of 2018. In the first quarter of 2019, selling expenses amounted to EUR 1.7 million (Q1 2018: EUR 0.8 million). General and administrative expenses increased from EUR 3.9 million in Q1 2018 to EUR 5.9 million in Q1 2019.

Earnings before interest and taxes (EBIT) amounted to EUR -23.6 million in the first quarter of 2019 (Q1 2018: EUR -19.0 million). The Proprietary Development segment reported an EBIT of EUR -25.0 million (Q1 2018: EUR -15.9 million). EBIT in the Partnered Discovery segment was EUR 5.5 million (Q1 2018: EUR 0.6 million). In Q1 2019, the consolidated net loss amounted to EUR -22.7 million (Q1 2018: EUR -19.5 million). The loss per share for the first quarter of 2019 was EUR -0.72 (Q1 2018: EUR -0.67).

At the end of Q1 2019, the Company had EUR 431.2 million in cash, reported on the balance sheet under the line items "cash and cash equivalents"; "financial assets at fair value through profit or loss"; and current and non-current "other financial assets at amortized cost". On December 31, 2018, the Group’s liquidity position amounted to EUR 454.7 million. The number of shares issued totaled 31,839,572 at the end of Q1 2019 (year-end 2018: 31,839,572).

Financial Guidance and Operational Outlook for 2019

For the financial year 2019, MorphoSys continues to expect Group revenues in the range of EUR 43 to 50 million. Expenses for proprietary development and technology development are expected to be in a corridor of EUR 95 to 105 million. The Company confirmed its guidance for earnings before interest and taxes (EBIT) of EUR -127 to -137 million. This guidance does not include a potential larger milestone payment for the start of a phase 3 clinical trial of MOR103/GSK3196165 that could occur in the course of 2019. The guidance also does not include revenues from potential future partnership or licensing agreements for MOR208 (tafasitamab) or any other compound that is in MorphoSys’s proprietary development. Effects from potential in-licensing or co-development deals for new development candidates are also not included in the guidance.

In its Proprietary Development segment, MorphoSys expects the following events and activities in 2019:

MOR208 (tafasitamab)

– L-MIND: Complete data evaluation for primary completion analysis for all 81 patients enrolled under the current study protocol of the fully recruited L-MIND trial in r/r DLBCL and present the data at the upcoming International Conference on Malignant Lymphoma (ICML) in Lugano in June.

– Regulatory: Complete submission of Biologics License Application (BLA) to U.S. FDA for MOR208 (tafasitamab) by year-end and continue interactions with National European Regulatory Authorities to explore possibilities for approval in Europe.

– B-MIND: Continue pivotal phase 3 study evaluating MOR208 (tafasitamab) plus bendamustine versus rituximab plus bendamustine in r/r DLBCL and conduct a pre-planned, event-driven, interim analysis of B-MIND, which is projected to take place in the second half of 2019.

– Regulatory: Planned discussions with the FDA regarding future assay validation procedures to be used in conjunction with the amended B-MIND study.

– COSMOS: Continue phase 2 trial of MOR208 (tafasitamab) plus idelalisib or venetoclax in r/r CLL/SLL and present data towards the end of 2019.

– Front-line DLBCL: Initiate phase 1b trial of MOR208 (tafasitamab) in H2 2019.

– Commercial activities: Continue set-up of commercial capabilities in the U.S. in order to prepare for expected commercialization of MOR208 (tafasitamab), assuming FDA approval.

MOR202

– MorphoSys: Prepare for and start an exploratory clinical trial of MOR202 in an autoimmune indication.

– I-Mab: Continue recently started pivotal development programs of MOR202 in multiple myeloma in the Chinese region.

MOR106

– Together with Galapagos, continue phase 2 intravenous IGUANA study, phase 1 subcutaneous bridging study and the recently started phase 2 GECKO trial towards primary completion under global licensing agreement with Novartis.

– Preparations for a Japanese ethno-bridging study in atopic dermatitis together with Galapagos.

MOR107: Continue preclinical investigation of MOR107 with a focus on oncology indications.

MOR103/GSK3196165: Based on announcements made by GSK earlier this year, the initiation of a phase 3 clinical trial of MOR103/GSK3196165 in rheumatoid arthritis by GSK is expected for the second half of 2019, which would trigger a milestone payment to MorphoSys.

In its Partnered Discovery segment, MorphoSys expects the following events in 2019:

According to information provided on clinicaltrials.gov, by the end of 2019 primary completion may be reached in up to 10 clinical trials in phases 2 and 3 from partners evaluating antibodies made using MorphoSys’s technology. This includes:

– a potentially pivotal phase 2b study by Mereo Pharma in osteogenesis imperfecta (brittle bone syndrome) of the HuCAL antibody setrusumab (BSP804) directed against the target molecule sclerostin (this antibody was generated within the scope of MorphoSys’s partnership with Novartis and subsequently licensed from Novartis to Mereo).

– further phase 3 trials of Tremfya(R) conducted by Janssen in psoriatic arthritis.

Whether, when and to what extent news will be published following the primary completion of trials in the Partnered Discovery segment is at the full discretion of MorphoSys’s partners.

MorphoSys will continue to support its proprietary development activities by evaluating potential in-licensing, co-development, and/or acquisition opportunities or the potential initiation of new proprietary development programs with the goal of maintaining and expanding the Company’s position in its current therapeutic and technological fields of activities.

On May 7, 2019 Castle Biosciences, Inc., a skin cancer diagnostics company providing personalized genomic information to improve cancer management decisions, reported two presentations at the 2019 American College of Mohs Surgery (ACMS) Annual Meeting held in Baltimore from May 2-5 (Press release, Castle Biosciences, MAY 7, 2019, View Source [SID1234535848]).

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Progress in the development of a prognostic gene expression profile test in cutaneous squamous cell carcinoma (cSCC) was highlighted in an oral presentation. The total number of deaths from cSCC, one of the most common cancers in the U.S., is approaching or surpassing that from melanoma. Many patients with cSCC will have a favorable prognosis, but 25-40% of high-risk subsets will experience metastasis or develop recurrences. Current cSCC staging systems are evolving but more accurate methods of risk prediction are needed to appropriately direct workup and treatment. The goal of this development program is to identify and validate a clinical test that improves upon existing clinicopathologic staging systems to identify patients who have a high risk for regional/distant metastasis and enable more informed clinical management decisions.

In an ongoing development study, primary cSCC specimens with associated clinical outcome data were accrued from 18 centers. The discovery phase of the program included determining genes identified for their expression in recurrent and non-recurrent tumors. Researchers successfully identified genes that exhibited significant differential expression in cSCC samples from patients who experienced a recurrence, including several specific to regional/distant metastasis. In an archival training cohort of 122 patients, gene expression data from 140 candidate genes were used to identify a preliminary gene set and predictive algorithm.

To assess the predictive value of this assay, Kaplan-Meier survival analysis was performed in an independent validation cohort of 107 patients. Results from the analysis support the predictive value of the test to identify two groups of patients with significantly different risk for regional/distant metastasis (p<0.0001). The positive predictive value of the test in this preliminary validation study was 60%, which compares favorably to the performance of current staging systems in this cohort.

Based on these preliminary validation results, an expanded validation program for the cSCC prognostic test is now underway, including additional archival studies and a prospective validation study.

"The continued progress toward validation of this prognostic test for cSCC demonstrates that improvements in risk identification based on tumor biology are feasible," said Sarah T. Arron, M.D., Ph.D., University of California San Francisco and the San Francisco VA Health System, an investigator in the study. "Clinical use of a validated prognostic test such as this could help inform clinical decisions on staging and adjuvant therapy, and improve upon currently used staging systems."

Second study presented at ACMS

A second study presented as a poster at ACMS highlighted results from a meta-analysis evaluating the performance of the DecisionDx-Melanoma gene expression profile test in four unique, independent patient cohorts.

Results from this meta-analysis with 1,479 patients from four independent cohorts confirm that the DecisionDx-Melanoma test is a significant, independent predictor of recurrence and metastasis in patients with Stage I-III melanoma. Patients identified as highest risk (Class 2B) by the DecisionDx-Melanoma test were 2.9 times more likely to experience recurrence than those identified as lowest risk (Class 1A, p<0.0001), independent of other clinicopathologic features. The meta-analysis, a statistical method considered to be among the highest level of evidence (Level 1A) for prognostic tests, supports the use of the DecisionDx-Melanoma gene expression profile test to inform patient management decisions.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is one of the most common cancers. Approximately 200,000 patients per year are diagnosed with cSCC with high-risk features. Most patients have a favorable prognosis, but a subset of patients will develop metastasis and up to 15,000 patients each year die from their disease. As current staging parameters have a low positive predictive value, many more patients are considered high risk than actually develop metastatic disease. Conversely, many patients who develop metastatic disease are misidentified as low risk. This may lead to over and undertreatment of a substantial number of cSCC patients. To address this clinical need, Castle Biosciences is developing a gene expression profile test designed to improve upon current staging systems and identify patients with cSCC at high risk for metastasis or recurrence, in order to enable more informed clinical decisions regarding adjuvant therapy and other management options.

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 2,900 patients. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multicenter studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in five prospective studies including more than 780 patients. The consistent high performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter study cohorts that included over 1,400 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in multicenter and single-center studies. More information about the test and disease can be found at www.SkinMelanoma.com.

On May 7, 2019 Genomic Health, Inc. (NASDAQ: GHDX) reported financial results and business progress for the quarter ended March 31, 2019 (Press release, Genomic Health, MAY 7, 2019, View Source [SID1234535864]).

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"In the first quarter of 2019, we delivered more than 17 percent overall revenue growth and $13.0 million in profit driven by significant growth across all key product areas," said Kim Popovits, chairman of the board, chief executive officer and president of Genomic Health. "Our first quarter performance was very strong, based in part on the impact of the landmark TAILORx trial results, which are continuing to drive increased Oncotype DX Breast Recurrence Score test usage both in the United States and globally. We expect to achieve double-digit revenue growth for the year with continued growth across key products and look forward to the national reimbursement decision in Germany for the Oncotype DX breast cancer test."

First Quarter Financial Results

Total revenue for the first quarter of 2019 was $108.8 million, compared with $92.6 million for the first quarter of 2018, an increase of 17.4 percent, and an increase of 18.0 percent on a non-GAAP constant currency basis. U.S. product revenue was $91.0 million for the first quarter of 2019, compared with $78.9 million for the first quarter of 2018, an increase of 15.4 percent.

Revenue delivered across key product areas was as follows:

U.S. invasive breast revenue from Oncotype DX Breast Recurrence Score tests was $79.8 million for the first quarter of 2019, compared with $71.0 million for the first quarter of 2018, an increase of 12.5 percent.
U.S. prostate test revenue from Oncotype DX Genomic Prostate Score (GPS) tests was $8.5 million for the first quarter of 2019, compared with $5.8 million for the first quarter of 2018, an increase of 46.6 percent.
International product revenue for the first quarter of 2019 was $17.8 million, compared with $13.8 million for the first quarter of 2018, an increase of 29.0 percent, and an increase of 32.9 percent on a non-GAAP constant currency basis.
Net income was $13.0 million, or $0.35 and $0.34 per share on a basic and diluted basis, respectively, for the first quarter of 2019, an improvement of $16.8 million, compared with a net loss of $3.8 million, or $0.11 per share on a basic and diluted basis, for the first quarter of 2018. Operating income was $11.5 million for the first quarter of 2019, an improvement of $15.9 million, compared with an operating loss of $4.4 million for the first quarter of 2018.

More than 37,580 Oncotype test results were delivered in the first quarter of 2019, an increase of 15.9 percent, compared with more than 32,440 test results delivered in the same period in 2018. Tests delivered across key product areas was as follows:

Oncotype DX Breast Recurrence Score tests delivered in the U.S. grew 9.4 percent in the first quarter of 2019, compared with the same period in 2018.
Oncotype DX Genomic Prostate Score tests delivered in the U.S. grew 24.5 percent in the first quarter of 2019, compared with the same period in 2018.
Oncotype DX international tests delivered grew 28.1 percent in the first quarter of 2019, compared with the same period in 2018 and represented approximately 25 percent of total test volume in the first quarter of 2019.
Recent Business Highlights

Presented results from five studies at the 16th St. Gallen International Breast Cancer Conference, including real-world evidence that reinforces the treatment paradigm established by the TAILORx trial. Additionally, two decision impact studies from the UK and the Czech Republic highlighted the value of Oncotype DX in personalizing and improving the quality of clinical decisions in patients with early-stage breast cancer, including those with node positive disease .
Multiple private insurers established new coverage for the Oncotype DX Genomic Prostate Score test, bringing the total number of U.S. covered lives to more than 114 million, including Medicare.
First private insurer established reimbursement for the Oncotype DX AR-V7 Nucleus Detect test, bringing the total number of U.S. covered lives to more than 61 million, including Medicare.
The National Comprehensive Cancer Network (NCCN) strengthened its prostate cancer guidelines, recommending the consideration of AR-V7 testing in metastatic castrate resistant prostate cancer (mCRPC) patients following abiraterone/enzalutamide to help guide the selection of further therapy.
Conference Call Details
To access the live conference call today, May 7, 2019, at 4:30 p.m. Eastern Time via phone, please dial (877) 303-7208 from the United States and Canada, or +1 (224) 357-2389 internationally. The conference call ID is 6535029. Please dial in approximately 10 minutes prior to the start of the call. To access the live and subsequently archived webcast of the conference call, go to the Investor Relations section of the company’s website at View Source Please connect to the website at least 15 minutes prior to the presentation to allow for any software download that may be necessary.

On May 7, 2019 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 March 31, 2019 and reported on corporate developments (Press release, Aptose Biosciences, MAY 7, 2019, View Source [SID1234535816]).

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The net loss for the quarter ended March 31, 2019 was $5.5 million ($0.14 per share) compared with $6.8 million ($0.23 per share) for the quarter ended March 31, 2018. Total cash and cash equivalents and investments as of March 31, 2019 were $17.0 million. Based on current operations, cash on hand and available sources of capital provide the Company with sufficient resources to fund research and development and operations into 1H 2020.

"With the FDA allowance of our IND for CG-806, our oral, first-in-class pan-FLT3/pan-BTK inhibitor, we entered the second quarter advancing two separate clinical programs with two well-differentiated, small molecule targeted agents for the treatment of patients with hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "I’m most pleased to announce that we have eleven clinical sites committed to our Phase 1 clinical trial with CG-806 and that we expect to dose our first patient soon. In preclinical studies, CG-806 demonstrated the ability to potently inhibit all wild type and mutant forms of BTK and FLT3 driver kinases and to suppress additional oncogenic signaling pathways upon which cancer cells rely for survival, yet with a precision that avoids targets typically associated with toxicity. In those studies, CG-806 has repeatedly shown superiority to other approved and development stage BTK inhbitors and FLT3 inhibitors. In addition,CG-806 demonstrated safety and tumor elimination in animal models of cancer. Our second compound, APTO-253, is the only clinical-stage molecule shown to directly inhibit expression of the MYC oncogene in a patient with acute myeloid leukemia (AML), without the myelosuppression common to many MYC targeting approaches. Both CG-806 and APTO-253 are investigational products that address unmet needs and substantial market opportunities in hematology."

Key Corporate Highlights

Phase 1 a/b CG-806 Clinical Trial – In March 2019, Aptose announced regulatory allowance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 a/b clinical trial program with CG-806, an oral, first-in-class small molecule inhibitor of all known forms of FLT3 and BTK kinases. CG-806 is being developed for the treatment of patients with select hematologic malignancies, including CLL/SLL and non-Hodgkin’s lymphomas (NHL), as well as for patients with relapsed/refractory AML and MDS. The IND allows for immediate testing of CG-806 in patients with certain relapsed or refractory B-cell malignancies, including CLL/SLL and NHL having wild type or C481S mutated forms of the BTK kinase. The first patient will receive 150 mg of oral CG-806 every 12 hours for 28 days. The second patient is planned to receive 300 mg every 12 hours for 28 days, and we anticipate six dose levels during the dose escalation phase of the study. Following identification of the recommended phase 2 dose, we plan to perform four separate expansion trials with up to 25 patients each from four different groups of B-cell malignancy patients. All of these patients will be assessed for safety, tolerance, PK, and a host of biomarkers and scans. Such analyses will characterize the safety and efficacy of CG-806 in this population of patients with B-cell malignancies. In addition, these analyses will inform the dose related plasma exposure levels of CG-806. Once a dose level achieves plasma concentrations that we believe will be therapeutic for AML patients, we plan to present the findings to the FDA and seek to initiate a separate Phase 1 trial for patients with AML and MDS. This strategy avoids treating the acutely ill AML patients to potentially non-efficacious doses and increases the likelihood that responses could be achieved rapidly in the AML/MDS patient population.

Phase 1b Clinical Study of APTO-253 | Favorable Tolerability and Inhibition of MYC Gene Expression in First Patient at Lowest Dose Level | Dosing Begins in Second Patient – Aptose previously announced that dosing had begun in the APTO-253 clinical trial in patients with relapsed or refractory hematologic malignancies. APTO-253 is the only known clinical-stage molecule that can directly inhibit expression of the MYC oncogene, shown to reprogram survival signaling pathways and contribute to drug resistance in many malignancies, including acute AML. The first patient in the trial tolerated the lowest dose of 20 mg/m2 of APTO-253 favorably. In addition, a reduction in MYC gene expression was observed, as well as the induction of p21, an indication of cell cycle arrest and apoptosis, and consistent with target engagement. Dosing of an MDS patient at the second dose level (40 mg/m2 APTO-253) has been initiated, and only one patient will be required at this dose level if no safety issues are observed. APTO-253 is being administered once weekly, over a 28-day cycle, and the study is expected to enroll up to 20 patients with relapsed or refractory AML and high-risk MDS patients. The study is designed to then transition to single-agent expansion cohorts in AML and MDS, followed by combination studies.

New Preclinical Data at AACR (Free AACR Whitepaper) – New preclinical data on CG-806 and APTO-253 were presented in separate poster presentations at the 2019 AACR (Free AACR Whitepaper) Annual Meeting in April. In studies that were conducted in collaboration with the Beat AML Initiative, CG-806 demonstrated significant potency across sub-groups of AML cells, and superior potency when compared to other FLT3 inhibitors, including midostaurin, sorafenib, sunitinib, dovitinib, quizartinib, crenolanib and gilteritinib. Sensitivity of patient cells with IDH1 R132 mutations was an unexpected finding. Additionally, in 28-day GLP toxicity and toxicokinetic studies, CG-806 continued to demonstrate a favorable safety profile. The poster highlights results of combination studies with CG-806 and venetoclax, which demonstrated enhanced killing of primary cancer cells from patients with AML and B-cell cancers. Researchers also presented in vitro studies of APTO-253 focused on its mechanism of action that involves targeting the MYC oncogene. Both AACR (Free AACR Whitepaper) posters are available on the Aptose website.

New $20MM Common Share Purchase Agreement with Aspire Capital Fund, LLC Replaces Prior Agreement – Aptose entered into a new Common Share Purchase Agreement (the "Agreement") with Aspire Capital Fund, LLC ("Aspire Capital") where Aspire Capital has committed to purchase up to $20MM of common shares of Aptose, at Aptose’s request from time to time, for up to 30 months. This Agreement replaces the agreement that Aptose entered into with Aspire Capital on May 30, 2018, which has been terminated by the parties. The Agreement is subject to approval by the Toronto Stock Exchange ("TSX") and NASDAQ, limits the amount of Aptose’s common shares that Aspire can own at one time to 9.99% of the issued and outstanding common shares of the Company, and limits the maximum number of common shares that can be issued under the Agreement to 19.99% of the Company’s outstanding common shares on the date of the Agreement unless shareholder approval is obtained or the shares issued to date once the 19.99% threshold is reached have an average purchase price equal to or exceeding $2.10.

Under the Agreement, no common shares will be sold on the TSX or on other trading markets in Canada. For the purpose of TSX approval, the Company intends to rely on the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible interlisted issuers on a recognized exchange, such as NASDAQ, provided that the transaction is being completed in compliance with the requirements of such other recognized exchange.

Upon receipt of the TSX and NASDAQ approval, as consideration for Aspire Capital’s obligation under the Agreement, Aptose will issue 171,428 common shares to Aspire Capital as a commitment fee.

Under the terms of the Agreement:
Aptose will control the timing and amount of the sale of common shares to Aspire Capital.
On any business day, Aptose shall have the right to direct Aspire Capital to purchase up to 200,000 common shares with a value not exceeding $500,000. However, upon mutual agreement, Aptose can direct Aspire Capital to purchase up to an additional 2,000,000 common shares.
The purchase price shall be equal to the lesser of: (i) the lowest sale price of the common shares on NASDAQ on the purchase date, or (ii) the average of the three lowest closing sale prices of the common shares on NASDAQ during the 10 business days prior to the purchase date.
In addition to the regular purchases, Aptose shall also have the right to require Aspire Capital to purchase up to an additional 30% of the trading volume of the common shares for the next business day at a purchase price (the "VWAP Purchase Price") equal to the lesser of: (i) the closing price of the common shares on NASDAQ on the VWAP purchase date, or (ii) ninety-seven percent (97%) of the VWAP purchase date’s volume weighted average price on NASDAQ (each such purchase, a "VWAP Purchase").
Aptose shall have the right, in its sole discretion, to determine a maximum number of common shares and set a minimum market price threshold for each VWAP Purchase and there are no limits on the number of VWAP purchases that Aptose may require.
For any business day that the closing sale price of the common shares on NASDAQ is below $0.25, the obligation of Aspire Capital to purchase common shares shall be automatically suspended for that business day only.

Research and development expenses of $3.3 million for the three-month period ended March 31, 2019 were comparable with $3.1 million for the comparative period. Changes to the components of our research and development expenses presented in the table above are primarily as a result of the following events:

In the three-month period ended March 31, 2019, program costs for our CG-806 consisted mostly of costs to complete the preclinical studies and prepare regulatory filings in support of an IND filing, and the manufacturing of drug product for the Phase 1clinical trial. In the comparative period, expenses reflected the completion of two dose range finding studies and the manufacturing of a batch of the drug substance to be used in toxicity studies.
In the three-month period ended March 31, 2019, program costs for our APTO-253 program consisted mostly of costs related to the Phase 1b clinical trial, and manufacturing costs for a second GMP batch of APTO-253. In the comparative period, the Company completed production of a GMP batch of drug product, and initiated necessary studies to present to the FDA in support of removing the clinical hold.
An increase in personnel expenses mostly related to additional clinical research staff to support two Phase 1 clinical trials.
A decrease in stock option compensation related mostly to stock options granted in the three-month period ended March 31, 2018, of which 100,000 with a grant date fair value of $2.03 vested immediately, contributing to higher expenses in that period.

General and administrative expenses of $2.3 million for the three-month period ended March 31, 2019 decreased by approximately $1.4 million compared with $3.7 million for the comparative period, primarily as a result of the following:

General and administrative expenses, excluding non-cash items, decreased by approximately $138.0 thousand, primarily as a result of higher professional and regulatory fees in support of financing activities in the three months ended March 31, 2018, and offset by higher travel, rent and salaries expense in the current period, in support of increased activities in the business.
Stock-based compensation decreased by approximately $1.3 million in the three months ended March 31, 2019, compared with the three months ended March 31, 2018 mostly related to approximately 1,059,000 stock options granted to directors, executive officers and general and administrative employees in the three-month period ended March 31, 2018, of which 750,000 with a grant date fair value of $2.03 vested immediately. In the current period, 1,024,000 stock options were granted to directors, executive officers and general and administrative employees with a grant date fair value of $1.29. Stock options granted by the Company during the three months ended March 31, 2019, vest over four years, except for 335,000 options which vest after one year.
Conference Call and Webcast

Aptose will host a conference call to discuss results for the year and three months ended March 31, 2019 today, Tuesday, May 7, 2019 at 5:00 PM ET. Participants can access the conference call by dialing 1-844- 882-7834 (North American toll free number) and 1-574-990-9707 (International) and using conference ID # 4879249. The conference call can be accessed here and will also be available through a link on the Investor Relations section of Aptose’s website at View Source 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 for seven days by dialing 1-855-859-2056, using the conference ID # 4879249.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended March 31, 2019 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

On May 7, 2019 Pfizer Inc. (NYSE: PFE) reported that the European Commission (EC) granted conditional marketing authorization for LORVIQUA (lorlatinib, available in the U.S., Canada and Japan under the brand name LORBRENA), as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI (Press release, Pfizer, MAY 7, 2019, View Source [SID1234535832]). LORVIQUA is a third-generation ALK TKI that was specifically developed to penetrate the blood brain barrier, in the presence or absence of resistance mutations.

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"Pfizer has worked to pioneer biomarker-driven medicine for patients with ALK-positive non-small cell lung cancer and we continue to advance patient care with the approval of LORVIQUA," said Andreas Penk, M.D., regional president, Oncology International Developed Markets at Pfizer. "We are proud that LORVIQUA is our second lung cancer medication approved in Europe within two months and our third biomarker-driven medicine for lung cancer. We look forward to making LORVIQUA available for European patients with ALK-positive non-small cell lung cancer who have progressed on prior therapy with a second generation ALK medicine."

The conditional marketing authorization was based on results from a non-randomized, dose-ranging and activity-estimating, multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating LORVIQUA for the treatment of patients with ALK-positive advanced NSCLC, who were previously treated with one or more ALK TKIs. A total of 139 patients with ALK-positive metastatic NSCLC after treatment with at least one second-generation ALK TKI, such as alectinib, brigatinib or ceritinib, were enrolled in the Phase 2 portion of the study. Among these patients, the overall response rate (ORR) for those who have been treated with one prior ALK TKI (N=28) was 42.9% (95% CI: 24.5, 62.8) and 39.6% (95% CI: 30.5, 49.4) for those with two or more prior ALK TKI treatments (N=111). In the trial, 67% of patients had a history of brain metastases.

"Over the last decade, our understanding of ALK-positive non-small cell lung cancer has advanced dramatically, leading to multiple medications for patients. However, the common challenges associated with treating the disease, including resistance and brain metastases have created an urgent need for additional treatment options," said Enriqueta Felip, M.D., Ph.D., Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology in Spain. "The LORVIQUA approval marks an exciting time in lung cancer innovation and I look forward to using this next-generation ALK inhibitor to treat my patients."

Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received LORVIQUA 100 mg once daily in study B7461001, the most common (≥ 20%) adverse reactions were hypercholesterolemia (84.4%), hypertriglyceridemia (67.1%), edema (54.6%), peripheral neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%), weight increased (26.4%), arthralgia (24.7%), mood effects (22.7%) and diarrhea (22.7%).

Conditional approval is granted to a medicinal product that fulfils an unmet medical need, where the benefit-risk balance is positive and the benefit of the product’s immediate availability outweighs the risk of less comprehensive data than normally required.1 Under the provisions of the conditional approval, Pfizer will provide additional data from the post-marketing studies, including the Phase 3 CROWN study of LORVIQUA versus crizotinib in the first-line treatment of patients with ALK-positive NSCLC, which is currently ongoing.

About LORVIQUA (lorlatinib)

LORVIQUA is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORVIQUA is approved in the EU as monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after:

alectinib or ceritinib as the first ALK TKI therapy; or
crizotinib and at least one other ALK TKI.
LORVIQUA is also approved:

Under the brand name LORBRENA in Japan for the treatment of ALK fusion gene-positive unresectable advanced and/or recurrent NSCLC with resistance or intolerance to ALK tyrosine kinase inhibitor(s).
Under the brand name LORBRENA in Canada, where it is conditionally approved as monotherapy for the treatment of adult patients with ALK-positive metastatic NSCLC who have progressed on: crizotinib and at least one other ALK inhibitor, or patients who have progressed on ceritinib or alectinib.
Under the brand name LORBRENA in the U.S. for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on:
crizotinib and at least one other ALK inhibitor for metastatic disease; or
alectinib as the first ALK inhibitor therapy for metastatic disease; or
ceritinib as the first ALK inhibitor therapy for metastatic disease.
The U.S. indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

LORBRENA (lorlatinib) IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Contraindications: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.

Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in 8% of subjects. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least 3 times during the first week after initiating LORBRENA. Depending upon the relative importance of each drug, discontinue LORBRENA or the CYP3A inducer for persistent Grade 2 or higher hepatotoxicity.

Central Nervous System (CNS) Effects: A broad spectrum of CNS effects can occur. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume at the same or reduced dose or permanently discontinue based on severity.

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332 patients who received LORBRENA. Eighty percent of patients required initiation of lipid-lowering medications, with a median time to onset of start of such medications of 21 days. Initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia. Monitor serum cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months after initiating LORBRENA, and periodically thereafter. Withhold and resume at same dose for the first occurrence; resume at same or reduced dose of LORBRENA for recurrence based on severity.

Atrioventricular (AV) Block: PR interval prolongation and AV block can occur. In 295 patients who received LORBRENA at a dose of 100 mg orally once daily and who had a baseline electrocardiography (ECG), 1% experienced AV block and 0.3% experienced Grade 3 AV block and underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA and periodically thereafter. Withhold and resume at reduced or same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of patients, including Grade 3 or 4 ILD/pneumonitis in 1.2% of patients. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis. Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity.

Embryo-fetal Toxicity: LORBRENA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective non-hormonal method of contraception, since LORBRENA can render hormonal contraceptives ineffective, during treatment with LORBRENA and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for 3 months after the final dose.

Adverse Reactions: Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). The most common (≥20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea; the most common (≥20%) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.

Drug Interactions: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Avoid concomitant use with moderate CYP3A inducers and strong CYP3A inhibitors. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as recommended. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the LORBRENA dose as recommended. Concomitant use of LORBRENA decreases the concentration of CYP3A substrates.

Lactation: Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.

Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of LORBRENA has not been established for patients with severe renal impairment.

Please see full prescribing information for LORBRENA in the U.S. here.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer worldwide, with more than two million new cases diagnosed globally in 2018.2 About 85 percent of all lung cancers are identified as non-small cell, and approximately 75 percent of these are metastatic, or advanced, at diagnosis.3

ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients.4,5 Epidemiology studies suggest that approximately three to five percent of NSCLC tumors are ALK-positive.6

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.