On August 6, 2019 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported business highlights and financial results for the second quarter ended June 30, 2019 (Press release, Fate Therapeutics, AUG 6, 2019, View Source [SID1234538189]).

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"The early safety and tolerability signals observed in patients receiving multiple doses of FT500, the first iPSC-derived cell therapy to undergo clinical investigation in the United States, are very encouraging. The ability to cost-effectively mass-produce a universal cell-based cancer immunotherapy, and to safely deliver that therapy ‘on demand’ in multiple doses, has the potential to transform outcomes for many patients," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We continue to be very pleased with the Company’s rapid pace of innovation, product development and leadership in bringing iPSC-derived cell-based immunotherapies engineered with potent anti-tumor functionality to cancer patients. Our first engineered iPSC-derived NK cell product candidate, FT516, is ready for Phase 1 clinical evaluation following successful completion of cGMP production, and the IND application for our multi-antigen targeted CAR19 NK cell product candidate, FT596, has been submitted to the FDA. Additionally, with the renewal of our collaboration with Memorial Sloan Kettering Cancer Center for the development of iPSC-derived T-cell immunotherapies, we are well positioned to continue to lead the field in the development of off-the-shelf CAR T-cell therapy."

Universal, Off-the-Shelf NK Cell Cancer Immunotherapy Clinical Programs

No DLTs Reported at 300M Cell Dose Level in FT500 Monotherapy Arm. The first three patients with advanced solid tumors have been treated with multiple doses of FT500, the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line, at the second dose level in the study’s monotherapy arm. All three patients received three weekly doses of FT500 at 300 million cells per dose in an outpatient setting, which treatment cycle was well-tolerated with no dose-limiting toxicities (DLTs) and no FT500-related serious adverse events reported by investigators. All three subjects were eligible to receive a second, multi-dose treatment cycle of FT500 at 300 million cells per dose.
No DLTs Reported at 100M Cell Dose Level in FT500 ICI Combination Arm. The first three patients with advanced solid tumors have been treated with multiple doses of FT500 in combination with immune checkpoint inhibitor (ICI) in the study’s combination arm. All three patients received three weekly doses of FT500 at 100 million cells per dose in an outpatient setting, which treatment cycle was well-tolerated with no dose-limiting toxicities and no FT500-related serious adverse events reported by investigators. All three subjects were eligible to receive a second, multi-dose treatment cycle of FT500 at 100 million cells per dose in combination with ICI.
FT516 cGMP Production Completed and Product Released for Clinical Trial Initiation. The Company completed final product release testing for FT516, a universal, off-the-shelf NK cell product candidate derived from a clonal master iPSC line engineered to express a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Starting with a single cryopreserved vial from a master engineered iPSC bank, hundreds of cryopreserved doses of FT516 were produced in a single cGMP campaign at a low cost per dose. The cryopreserved FT516 cell product met stringent post-thaw release specifications, including identity, purity, viability and functional activity. The Company is currently initiating clinical investigation of FT516 as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of B-cell lymphoma. FT516 is the first-ever cell product in the world derived from a genetically engineered pluripotent stem cell to be cleared for clinical investigation.
Universal, Off-the-Shelf NK Cell and T-cell Cancer Immunotherapy Preclinical Pipeline

Submitted IND for FT596 Multi-Antigen Targeted CAR NK Cell. FT596 is the Company’s first universal, off-the-shelf chimeric antigen receptor (CAR) NK cell product candidate, and is uniquely designed to engage multiple tumor-associated antigens expressed on cancer cells for best-in-class activity. The product candidate is derived from a master iPSC line engineered to express three functional anti-tumor components: a proprietary CAR targeting the B-cell antigen CD19; a novel hnCD16 Fc receptor for augmented antibody-dependent cellular cytotoxicity; and a unique IL-15 receptor fusion for enhanced NK cell activity. The Company submitted its Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for clinical investigation of FT596 as a monotherapy and in combination with monoclonal antibody therapy for the treatment of subjects with advanced B-cell lymphomas and advanced chronic lymphocytic leukemia.
Renewed iPSC-derived T-cell Collaboration with MSK. Under its collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair, the Company is currently conducting IND-enabling activities for FT819, its first universal, off-the-shelf CAR T-cell product candidate. FT819 is derived from a clonal master engineered iPSC line having complete elimination of T-cell receptor (TCR) expression and insertion of a novel 1XX CAR targeting CD19 into the T-cell receptor alpha (TRAC) locus. The three-year renewal extends the Company’s exclusive collaboration with Dr. Sadelain for the research and development of iPSC-derived T-cell product candidates.
Corporate Highlights

Received New U.S. Patent for CAR-encoded iPSCs. In May 2019, the U.S. Patent and Trademark Office granted to the Company a patent foundational to off-the-shelf, iPSC-derived CAR T-cell therapy. U.S. Patent Number 10,287,606, entitled "Genomic Engineering of Pluripotent Cells," covers iPSCs having a CAR construct encoded into the TRAC locus and an endogenous TCR alpha gene knocked out. The complete elimination of the endogenous TCR gene is critical in allogeneic CAR T-cell therapy to ensure the prevention of graft-versus-host disease, a life-threatening disease that can occur when donor T-cells attack a patient’s healthy tissue.
Expanded Board of Directors. In July 2019, the Company appointed Dr. Shefali Agarwal to its Board of Directors. Dr. Agarwal has nearly two decades of leadership experience across clinical development, medical research, clinical operations, regulatory, and medical affairs in oncology, and is currently the Chief Medical Officer of Epizyme, Inc., a clinical-stage company developing novel epigenetic therapies for cancer and other serious diseases.
Second Quarter 2019 Financial Results

Cash & Short-term Investment Position: Cash, cash equivalents and short-term investments as of June 30, 2019 were $162.0 million, compared to $201.0 million as of December 31, 2018. The decrease was driven primarily by the Company’s use of cash to fund operating activities.
Total Revenue: Revenue was $2.8 million for the second quarter of 2019, compared to $1.0 million for the same period in 2018. Revenue was derived primarily from the Company’s collaboration with Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $21.6 million for the second quarter of 2019, compared to $16.8 million for the same period in 2018. The increase in R&D expenses was attributable primarily to an increase in employee compensation, including share-based compensation, and in expenses associated with the clinical development and manufacture of the Company’s product candidates and the conduct of our research activities including under our collaboration agreements.
G&A Expenses: General and administrative expenses were $5.3 million for the second quarter of 2019, compared to $3.8 million for the same period in 2018. The increase in G&A expenses was attributable primarily to an increase in employee compensation, including share-based compensation.
Shares Outstanding: Common shares outstanding were 65.3 million as of June 30, 2019 and 64.7 million as of December 31, 2018. Preferred shares outstanding as of June 30, 2019 and December 31, 2018 were 2.8 million, each of which is convertible into five shares of common stock.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Tuesday, August 6, 2019 at 5:00 p.m. ET to review financial and operating results for the quarter ended June 30, 2019. In order to participate in the conference call, please dial 877-303-6235 (domestic) or 631-291-4837 (international) and refer to conference ID 3898842. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is fraught with batch-to-batch and cell-to-cell variability that can affect safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 200 issued patents and 150 pending patent applications.

About FT500
FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. Despite the clinical benefit conferred by approved immune checkpoint inhibitor (ICI) therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or progress on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations. FT500 is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (clinicaltrials.gov ID number NCT03841110). The study is designed to assess the safety and activity of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved ICI therapies – nivolumab, pembrolizumab or atezolizumab – in patients that have failed prior checkpoint inhibitor therapy. Patients who are clinically stable following the first cycle of FT500 treatment are eligible to receive a second treatment cycle of three additional once-weekly doses of FT500.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity (158V), non-cleavable CD16 (hnCD16) Fc receptor. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. CD16 occurs in two variants, either with high (158V) or low (158F) affinity for the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the CD16 high-affinity variant, which is present in approximately 15% of patients, have improved clinical outcomes. In addition, ADCC is dependent on NK cells maintaining active levels of CD16 expression, and the expression of CD16 on NK cells has been shown to undergo considerable down-regulation in cancer patients, which can significantly inhibit anti-tumor activity. FT516 incorporates a novel CD16 Fc receptor, which has been modified to prevent its down-regulation and augment its binding to tumor-targeting antibodies for enhanced ADCC. The FDA has allowed investigation of FT516 in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of B-cell lymphoma (clinicaltrials.gov ID number NCT04023071).

On August 6, 2019 Neon Therapeutics, Inc. (Nasdaq: NTGN), a clinical-stage immuno-oncology company developing neoantigen-based therapeutics, reported financial results for the second quarter ended June 30, 2019 and provided a business update (Press release, Neon Therapeutics, AUG 6, 2019, View Source [SID1234538206]).

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"We continue to make important progress across Neon’s programs as we continue to advance our leadership in the field of neoantigen-bases therapies. In recent months, we made important steps forward, including the release of the top-line data from our NT-001 trial of NEO-PV-01 that demonstrated consistent prolongation of progression-free survival across all three tumor types compared with historical checkpoint inhibitor monotherapy studies. We are also proud that the FDA recently cleared the IND for our off-the-shelf neoantigen vaccine candidate, NEO-SV-01," said Hugh O’Dowd, Neon’s Chief Executive Officer. "In the months ahead, we look forward to presenting detailed data from our NT-001 trial at a fall medical society meeting, including potential immune correlates and biomarker-selection strategies that could guide Phase 2 development, and also to completing process development work that will enable our planned CTA filing in Europe for our personal neoantigen T cell therapy candidate, NEO-PTC-01."

Pipeline Updates

Neon is developing neoantigen-targeting therapies across multiple treatment modalities, including both personal and precision vaccine and T cell therapy candidates.

NEO-PV-01: Neon’s investigational personal neoantigen vaccine, NEO-PV-01, is custom-designed and manufactured based on the unique mutational fingerprint of each individual patient. NEO-PV-01 is being studied in multiple ongoing Phase 1b clinical trials.

NT-001 Trial: Neon’s ongoing, multicenter Phase 1b clinical is evaluating a combination of NEO-PV-01 with OPDIVO (nivolumab) in patients with metastatic melanoma, smoking-associated non-small cell lung cancer (NSCLC) or bladder cancer.

In July, Neon announced top-line results from 82 patients in the NT-001 trial, with at least 12-month median follow-up in each of the three cohorts.

Across all three distinct tumor types, the results demonstrated prolonged and consistent improvements in progression-free survival (PFS) that compare favorably to those observed with checkpoint inhibitor monotherapy, based on historical benchmark data. At 13.4-month median follow-up in 34 patients with metastatic melanoma, the median PFS had not yet been reached; in 27 patients with metastatic NSCLC, median PFS was 5.6 months; and in 21 patients with metastatic bladder cancer, median PFS was 5.6 months.

No serious adverse events were observed that were related to the NEO-PV-01/OPDIVO combination. Low grade adverse events attributable to the NEO-PV-01/OPDIVO combination included injection site reactions, fatigue and influenza-like illness.

These top-line data, which come from the 82 patients in the Intention-to-Treat population who received at least one dose of OPDIVO in the Phase 1b NT-001 trial, support further development of NEO-PV-01, including randomized Phase 2 trials of NEO-PV-01 in metastatic disease settings.

Neon plans to present more detailed data from its NT-001 clinical trial at an upcoming medical society meeting.

NT-002 Trial: In April, Neon completed enrollment in NT-002, its Phase 1b clinical trial evaluating NEO-PV-01 in combination with the current standard of care, KEYTRUDA (pembrolizumab) and chemotherapy, in first-line patients with untreated advanced or metastatic NSCLC. This trial is evaluating the safety, tolerability and efficacy of NEO-PV-01 in the metastatic setting. Neon expects to report immune monitoring and clinical outcome data from this trial by the end of Q3 2020.

NT-003 Trial: This Phase 1b clinical trial of NEO-PV-01 in metastatic melanoma combinations is currently enrolling. NT-003 will evaluate NEO-PV-01 and OPDIVO in combination with other agents, including Apexigen’s CD40 agonist (APX005M) or a CTLA-4 antagonist, to further enhance any NEO-PV-01-induced neoantigen immune response and improve clinical outcomes. This trial will also evaluate alternative NEO-PV-01 dosing schedules. Neon plans to announce immune monitoring data from this study in the second half of 2020.

NEO-PTC-01: Neon’s personal adoptive T cell therapy candidate consists of multiple T cell populations targeting neoantigens that are predicted to be the most therapeutically relevant from each patient’s tumor. NEO-PTC-01 uses T cells from the periphery of each patient that are then primed, activated and expanded to generate a therapy that specifically targets that patient’s personal neoantigens, with the potential to drive a robust and persistent anti-tumor response.

CTA Filing: Building on success to date in generating both memory and de novo immune responses, Neon is completing process development, which supports its plan to file a CTA in Europe in the second half of 2019 to evaluate NEO-PTC-01 in refractory solid tumor settings. This work is being performed in collaboration with the Netherlands Cancer Institute (NKI), a leading academic research and treatment center with expertise in T cell biology and treatments.

NEO-SV-01: Neon is planning to develop its off-the-shelf neoantigen vaccine for the treatment of a genetically-defined subset of hormone receptor-positive (HR+) breast cancer, potentially across disease stages, in combination with hormonal, chemotherapy or targeted therapies.

IND Clearance: Neon reported that the U.S. Food & Drug Administration (FDA) has cleared Neon’s IND application for NEO-SV-01.

Expected Milestones

NEO-PV-01: Clinical results and correlative immune data from NT-001 Phase 1b trial planned for presentation at a medical congress (2H 2019)

NEO-PTC-01: Planned European CTA filing to evaluate NEO-PTC-01 in a refractory solid tumor setting (2H 2019)

NEO-PV-01: Planned clinical results and correlative immune data, including 12-month follow-up, from NT-002 Phase 1b trial in first-line metastatic NSCLC (Q3 2020)

NEO-PTC-01: Planned Phase 1 initiation in a refractory solid tumor setting (Q2 or Q3 2020)

NEO-PV-01: Planned immune data from NT-003 Phase 1b trial in metastatic melanoma combinations (2H 2020)

NEO-PV-01: Planned Phase 2 initiation of randomized clinical trial in first-line metastatic melanoma (2020)

Second Quarter 2019 Financial Results and Financial Guidance:

R&D Expenses: Research and development expenses were $16.7 million for the second quarter of 2019, compared to $14.8 million for the same period last year. The increase was primarily due to costs related to continued research and development of NEO-PV-01, NEO-PTC-01 and NEO-SV-01, as well as investments in R&D headcount to support the advancement of Neon’s pipeline.

G&A Expenses: General and administrative expenses were $5.6 million for the second quarter of 2019, compared to $4.3 million for the same period last year. The increase was primarily due to personnel-related costs, expenses associated with intellectual property protection and costs associated with being a public company.

Net Loss: Net loss was $21.9 million for the second quarter of 2019, compared to $18.9 million for the same period last year.

Cash Position: As of June 30, 2019, cash, cash equivalents and marketable securities were $61.0 million, as compared to cash, cash equivalents and marketable securities of $103.3 million as of December 31, 2018.

Financial Guidance: Based on its current operating plan, Neon expects that its existing cash, cash equivalents and marketable securities will enable the Company to fund its anticipated operating expenses and capital expenditure requirements into June 2020.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

On August 6, 2019 Novocure (NASDAQ: NVCR) reported that it will participate in three upcoming investor conferences (Press release, NovoCure, AUG 6, 2019, View Source [SID1234538222]).

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Pritesh Shah, Novocure’s Chief Commercial Officer, will participate in the Wedbush PacGrow Healthcare Conference on August 14, 2019, in New York City. Mr. Shah’s presentation will begin at 8:35 a.m. EDT. Mr. Shah will also participate in one-on-one meetings with investors throughout the day.

Additionally, Wilco Groenhuysen, Novocure’s Chief Financial Officer, will participate in the 2019 Wells Fargo Securities Healthcare Conference on September 4, 2019, in Boston. Mr. Groenhuysen’s presentation will begin at 1:15 p.m. EDT. Mr. Groenhuysen will also participate in one-on-one meetings with investors throughout the day.

Lastly, Mike Ambrogi, Novocure’s Chief Operating Officer, will participate in Baird’s 2019 Global Healthcare Conference on September 5, 2019, in New York City. Mr. Ambrogi’s presentation will begin at 12:15 p.m. EDT. Mr. Ambrogi will also participate in one-on-one meetings with investors throughout the day.

A live audio webcast of the presentations can be accessed from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for replay for at least 14 days following the events.

Novocure’s corporate presentation is updated periodically, and the current presentation can be accessed from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations.

On August 6, 2019 MorphoSys Discloses Biomarker to Stratify Patient Population in B-MIND Study of Tafasitamab plus Bendamustine in r/r DLBCL (Press release, MorphoSys, AUG 6, 2019, View Source [SID1234538248]).

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MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ: MOR) reported specifications of the biomarker that was implemented in the currently ongoing phase 3 B-MIND study. B-MIND compares the efficacy of tafasitamab (MOR208) plus bendamustine versus rituximab plus bendamustine in patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL). The biomarker, which is the basis for a co-primary endpoint, is described as a low baseline peripheral blood natural killer (NK) cell count and was implemented in agreement with the FDA as an amendment of B-MIND in the first quarter of this year.

Patients with a low number of NK cells (defined as 100 or fewer NK cells per microliter blood) at study entry represent approximately 50% of the overall study population and are believed to exhibit a less favorable response to anti-CD20-based therapies. Pre-clinical data generated at MorphoSys suggests that tafasitamab’s potential to more efficiently recruit effector cells, predominantly NK cells, may therefore be of particular benefit for this patient population.

The co-primary endpoint allows for efficacy testing in the overall patient population as originally planned, and also in those patients with a low NK cell count at baseline. An event-driven interim analysis is expected to occur in Q4 2019 following a longer than expected duration of response in the overall patient population.

"Patients with r/r DLBCL who are not eligible for high dose chemotherapy and autologous stem cell transplantation have a poor prognosis, which is even worse for patients who are characterized by a low baseline NK cell count. The enhanced NK cell recruitment that tafasitamab is believed to exert through its ENFORCERTM format may activate even minimal NK cell numbers, which could potentially translate into enhanced activity against tumor cells," said Dr. Malte Peters, Chief Development Officer of MorphoSys AG. "The amendment of the B-MIND study allows us to test this hypothesis and potentially to provide a benefit for a distinct patient population that does not have targeted treatment alternatives."

About B-MIND
The phase 3 B-MIND study is designed to investigate the CD19 antibody tafasitamab in combination with bendamustine versus a combination of the CD20 antibody rituximab plus bendamustine in patients with r/r DLBCL who are not eligible for high dose chemotherapy and autologous stem cell transplantation. The biomarker had been implemented in agreement with the FDA in the first quarter of 2019. The pre-planned, event-driven interim analysis of B-MIND is expected to take place in the fourth quarter of 2019. In case the overall study population passes the futility analysis, an event-driven primary analysis of the study is expected in late Q1 2020. In case the overall study population fails, but the biomarker subpopulation passes the futility analysis, the study will continue, but an increase from 330 to 450 patients is required, in which case an event-driven primary analysis of the study is expected in Q1 of 2021. Only if both groups do fail the interim analysis for futility the overall study can be considered futile.

On August 6, 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 June 30, 2019 and reported on corporate developments (Press release, Aptose Biosciences, AUG 6, 2019, View Source [SID1234538190]).

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The net loss for the quarter ended June 30, 2019 was $6.2 million ($0.13 per share) compared with $10.3 million ($0.30 per share) for the quarter ended June 30, 2018. Total cash and cash equivalents and investments as of June 30, 2019 were $35.4 million. Based on current operations, cash on hand and committed capital provide the Company with sufficient resources to fund all planned Company operations including research and development into 2H 2020.

"Aptose now is clinically testing two well-differentiated and targeted small molecules in patients with devastating hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "CG-806, our first-in-class pan-FLT3/pan-BTK multi-cluster kinase inhibitor, commenced dosing in a Phase 1a/b dose-escalation study in patients with B cell malignancies that have failed or are intolerant to standard therapies. Our first patient, who previously had failed multiple other therapies, now is receiving 150 mg capsules of CG-806 orally twice daily and thus far has reported no drug-related adverse events. In addition to safety and pharmacokinetics, we are monitoring for signs of biomarker movement that may indicate target engagement."

Dr. Rice continued, "In addition, our APTO-253 Phase 1b trial for patients with relapsed / refractory acute myeloid leukemia (or AML) and myelodysplastic syndrome (or MDS) is proceeding smoothly. We completed dosing in the first two cohorts, with the third cohort well under way. APTO-253 is the only known clinical-stage molecule that directly can inhibit expression of the MYC oncogene, shown to contribute to drug resistance in many malignancies. Initial data from our patients in all three cohorts demonstrated MYC inhibition, and this is true both for patients with AML and MDS. We are pleased to be treating patients with both of our distinguishing pharmaceutical assets and are hopeful that clinical testing will prove them to be effective therapies for hematologic malignancy patients greatly in need of new treatment options."

Key Corporate Highlights

Phase 1 a/b CG-806 Clinical Trial – First CLL Patient Dosed – Aptose recently reported the initiation of dosing in the CG-806 clinical trial. The Phase 1a/b multicenter, open-label, dose-escalation clinical trial of CG-806 is designed to assess safety, tolerability, pharmacokinetics and pharmacodynamic responses of CG-806 treatment; preliminary efficacy of CG-806; and establish the recommended Phase 2 dose. Aptose is conducting the Phase 1 trial with orally administered CG-806 in ascending doses to patients with relapsed or refractory B cell malignancies, including CLL or non-Hodgkin lymphomas (NHL). The first subject on the trial is a CLL patient that previously failed ibrutinib, venetoclax, rituximab and idelalisib, and that patient now has successfully received more than 50 doses of CG-806. The second patient to be enrolled is planned to receive oral doses of 300mg twice daily. Currently, eight U.S. sites are open for screening and enrolling patients for the study, with ten additional sites scheduled to come on board in the near future. More information is available at www.clinicaltrials.gov (here).

Phase 1b Clinical Study of APTO-253 – Demonstrates Inhibition of MYC Oncogene in AML and MDS Patients – Aptose has completed dosing of the first two cohorts in a Phase 1b trial with MYC inhibitor APTO-253, with only one patient required in each cohort. In addition, two patients have completed cohort three at 66mg/m2. As the Company reported, MYC biomarker data are available currently for three of the patients, all of whom completed the 28-day cycle and experienced reductions of MYC gene expression in their peripheral blood cells, an important finding as MYC plays a central role in the oncogenic process. The Phase 1b, multicenter, open-label dose-escalation clinical trial of APTO-253 is designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamic responses and establish the recommended Phase 2 dose and efficacy of APTO-253 as a single agent. APTO-253 is being administered once weekly, over a 28-day cycle. The study is expected to enroll up to 20 patients with relapsed or refractory AML and high-risk MDS patients. The dose escalation portion of the study is enrolling efficiently and is designed to then transition, as appropriate, to single-agent expansion cohorts in AML and MDS, followed by combination studies. More information can be found at www.clinicaltrials.gov (here).

New Preclinical Data at EHA (Free EHA Whitepaper) – CG-806 Suppressed Tumor Growth in Preclinical Models – In June, new preclinical data on CG-806 were presented in a poster at the 24thCongress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Amsterdam, the Netherlands. The poster highlighted the in vivo anti-leukemic efficacy of CG-806 and its GLP toxicology and toxicokinetic profile. In a preclinical MV4-11 FLT3-ITD AML xenograft mouse model, CG-806 suppressed leukemia growth at all doses tested throughout the 28-day period of dosing. After dosing was halted, 5 of 11 (45%) mice treated with 100 mg/kg were cured through day 120, and 10 of 11 (91%) mice treated with 300 mg/kg group were cured, with no observed toxicities. Retreating the "uncured’ mice in these two dose groups for an additional 28 days beginning on day 88 led to rapid and robust antitumor responses resulting in "cures" in all retreated mice through day 120. In the "re-treated" mice, no drug resistance and no toxicities were observed. Consistent with the tolerability of CG-806 in murine xenograft studies, orally administered CG-806 was well tolerated in 28-day GLP safety, PK and toxicokinetic studies in mice and dogs, as well as in separate respiratory, neurological and cardiovascular safety studies.

Financial Update – Since the last quarterly update, Aptose announced the closing of an underwritten public offering of 11,500,000 common shares of the Company (the "Common Shares") at a price to the public of $1.85 per Common Share, including the exercise in full by the underwriters of their option to purchase 1,500,000 additional Common Shares. The gross proceeds from the offering, before deducting the underwriting discounts and commissions, were approximately $21.3 million. Additionally, the Company entered into a new "at-the-market," or ATM, agreement for $40 million with Piper Jaffray and Canaccord Genuity as co-agents, to issue and sell Common Shares of Aptose through ATM distributions on Nasdaq. This ATM replaces the Company’s previous ATM program. Finally, as previously announced, Aptose entered into a new $20 million Common Shares Purchase Agreement with Aspire Capital Fund, LLC ("Aspire Capital"), which replaces the prior agreement between the parties, pursuant to which Aspire Capital has committed to purchase up to $20 million of Common Shares of Aptose, at Aptose’s request from time to time, for up to 30 months. Both of these financing vehicles can be accessed under the sole discretion of Aptose, and the company can determine the time, price and number of shares to be sold, if any.
A summary of the results of operations for the three and six months ended June 30, 2019 and 2018 is presented below:

The net loss for the three-month period ended June 30, 2019 decreased by approximately $4.1 million to $6.2 million as compared with $10.3 million for the comparable period. The decrease is primarily as a result of $5 million in license fees for CG-806 paid in the comparable period, lower professional fees related to regulatory filings in the comparable period in support of financing activities and offset by higher operational costs (such as rent, salaries and travel) associated with having two molecules in clinical development.

The net loss for the six-month period ended June 30, 2019, decreased by $5.4 million to $11.7 million compared with $17.1 million for the comparable period. Year-to-date results were impacted by similar factors to those noted above.

Research and Development
The research and development expenses for the three and six months ended June 30, 2019 and 2018 are as follows:

Research and development expenses decreased by $4.3 million to $3.5 million for the three-month period ended June 30, 2019 as compared with $7.8 million for the comparative period. Research and development expenses decreased by $4.2 million to $6.8 million for the six-month period ended June 30, 2019 as compared with $11.0 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:

We paid a total of $5 million in license fees to CG in the three-month period ended June 30, 2018, which is comprised of $2 million for the Rights to CG-806 and $3 million for the China Rights. CG 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 three-month period ended March 31, 2019, program costs consisted mostly of costs to complete the preclinical studies and to prepare regulatory filings in support of an IND filing, and the manufacturing of drug product for the Phase 1 clinical trial. In the three-month period ended June 30, 2019, program costs consisted mostly of contractors in support of the B cell malignancy clinical trial, which was approved by the FDA in March 2019, and in ongoing manufacturing costs of CG-806 to supply the trial. In the period ended March 31, 2018, program costs 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 June 30, 2018, we manufactured a GLP batch of CG-806 to be used in toxicity studies, we initiated the manufacturing of a GMP batch of the drug substance for future clinical trials, and we initiated a toxicity study in rodents.
In the three-month period ended June 30, 2019, program costs for APTO-253 consisted mostly of costs associated with the clinical trial, which was actively enrolling patients during this period. 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 three-month period ended March 31, 2018, 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. 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.
An increase in personnel expenses mostly related to additional clinical research staff to support two Phase 1 clinical trials.
For the six-month period ended June 30, 2019, there was a decrease in stock option compensation of approximately $243 thousand as compared with the six-month period ended June 30, 2018, 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
The general and administrative expenses for the three and six months ending June 30, 2019 and 2018 are as follows:

General and administrative expenses of $2.9 million for the three-month period ended June 30, 2019 increased by approximately $0.3 million compared with $ 2.5 million for the comparative period, primarily as a result of higher personnel related expenses, increased travel, higher legal and regulatory fees and rent and office costs and offset by lower share based payment expenses associated with financing activities.

General and administrative expenses decreased in the six-month period ended June 30, 2019 as compared with the six month period ended June 30, 2019, mostly as a result of lower stock option compensation recorded in the current period and offset by higher expenses related to personnel, travel, rent and office costs, legal and regulatory expenses.

General and administrative expenses (excluding non-cash items) increased in the three and six months ended June 30, 2019, compared with the three and six months ended June 30, 2018, primarily as a result of increased headcount, higher consulting fees and professional fees, rent and office and travel expenses in support of financing activities and in support of increased company-wide operations.

In the three-month period ended June 30, 2019, we issued 171,428 Common Shares (the "Commitment Shares") to Aspire Capital as a commitment fee for entering into the Common Shares Purchase Agreement that we entered with Aspire Capital in 2019. We recorded $360 thousand in general and administrative expenses related to the issuance of these Commitment Shares. In the three-month period ended June 30, 2018, we issued 170,261 Common Shares to Aspire Capital as a commitment fee for entering into our prior Common Shares Purchase Agreement with Aspire Capital in 2018. We recorded $600 thousand in general and administrative expenses related to the issuance of these Common Shares.

Stock option compensation for the three-month period ended June 30, 2019 was comparable with the stock option compensation recorded in the three month period ended June 30, 2018. For the six-month period ended June 30, 2019, stock-based compensation decreased by approximately $1.3 million compared with the six-month period ended June 30, 2018, mostly related to 750,000 stock options with a grant date fair value of $2.03 vested immediately that were granted to directors and executive in the three-month period ended March 31, 2018. We granted a total of 1,105,000 stock options to directors and general and administrative employees in the six-month period ended June 30, 2019 with an average grant date fair value of $1.29 as compared with a total of 1,722,500 stock options with an average grant date fair value of $2.13 in the six-month period ended June 30, 2018. In addition, we granted 80,000 restricted share units ("RSUs") in the current six month period as compared with nil in the comparative six-month period.

Conference Call and Webcast

Aptose will host a conference call to discuss results for the three and six months ended June 30, 2019 today, Tuesday, August 6, 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 # 5090577. 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 # 5090577.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended June 30, 2019 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

Note

The information contained in this news release is unaudited.