On November 10, 2020 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, tumor-agnostic therapies, reported financial results for the third quarter ended September 30, 2020 and provided a corporate update (Press release, Black Diamond Therapeutics, NOV 10, 2020, View Source [SID1234570444]).

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"At Black Diamond, we are leveraging our proprietary MAP platform to pioneer a differentiated approach to drug development, in which we aggregate novel oncogenic driver mutations into druggable families enabling the design of potent and selective MasterKey inhibitor product candidates," said David M. Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "This MasterKey profile extends not only to our lead product candidate BDTX-189, which is currently progressing through Phase 1/2 clinical development, but also throughout our early-stage pipeline. We believe the addition of Rachel Humphrey to our executive team to shepherd these programs through the clinic, as well as the appointment of Bob Ingram as Chairman of our Board to lend his leadership and industry expertise, will enable us to realize the potential of our science and to deliver precision medicines to patients who currently lack targeted treatment options."

Recent Developments

Black Diamond continued to enroll and dose patients in the MasterKey-01 study, a Phase 1/2 clinical trial of BTDX-189. The Company remains on track to complete the Phase 1 portion of the trial in the first half of 2021.
In October 2020, Black Diamond presented pre-clinical data on BDTX-189 at the 32nd Annual EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Virtual Symposium:
In cell-based assays, BDTX-189 achieved potent inhibition of 48 ErbB mutant variants, including the family of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) Exon 20 insertion mutations, while maintaining selectivity vs. wild-type EGFR (WT-EGFR).
The potency and selectivity profile for BDTX-189 against a selection of allosteric EGFR and HER2 mutations was compared to that of other currently approved ErbB tyrosine kinase inhibitors (TKIs) and with ErbB TKIs currently in clinical development. BDTX-189’s selectivity compared favorably with the other inhibitors evaluated, which either lacked potency against the broad panel of allosteric ErbB mutant oncogenes or did not achieve targeted selectivity vs. WT-EGFR.
Pre-clinical evaluation of BDTX-189’s pharmacokinetic (PK) profile revealed that BDTX-189 achieved the desired rapid and sustained target occupancy with rapid clearance.
BDTX-189 demonstrated dose-dependent tumor inhibition and regression in both engineered HER2 S310F tumor models and in EGFR Exon 20 insertion patient-derived xenograft models.
Black Diamond continued to advance its program in glioblastoma multiforme (GBM) toward nomination of a development candidate, as well as its early-stage pipeline programs derived from the Company’s Mutation-Allostery-Pharmacology (MAP) platform.
In September 2020, Black Diamond appointed biopharmaceutical veteran Robert A. Ingram as Chairman of its Board of Directors.
In September 2020, Black Diamond strengthened its executive team with the appointment of Rachel Humphrey, M.D., as Chief Medical Officer.
Financial Highlights

Black Diamond ended the third quarter of 2020 with $333.1 million in cash, cash equivalents, and investments, compared to $78.7 million for the third quarter of 2019. Net cash used in operations was $11.5 million for the third quarter of 2020 compared to $5.3 million for the third quarter of 2019.
Research and development (R&D) expenses were $12.9 million for the third quarter of 2020 compared to $5.6 million for the third quarter of 2019. The increase in R&D expenses was primarily related to an increase in headcount and external fees related to the development of our MAP platform and our product candidates, including BDTX-189.
General and administrative (G&A) expenses were $5.6 million for the third quarter of 2020 compared to $2.5 million for the third quarter of 2019. The increase in G&A expenses was primarily due to increased headcount and higher legal and other professional fees due to operating as a public company.
Upcoming Events

The Company will present pre-clinical data on Black Diamond’s GBM program at the Society of Neuro-Oncology 2020 Annual Meeting, taking place November 19-21, 2020:
Abstract Title: Potent, selective, and brain penetrant inhibitors of extracellular domain EGFR oncogenic mutants expressed in GBM demonstrate efficacy in an intracranial patient derived xenograft model
Abstract ID: EXTH-59
Session: Experimental and Translation Sciences Session III
David M. Epstein, Ph.D., President and CEO of Black Diamond, will present at the Jefferies Virtual London Healthcare Conference on Wednesday, November 18, 2020, at 2:40 PM GMT/9:40 AM ET.
About MasterKey-01

MasterKey-01 (NCT04209465) is a combined Phase 1/2 open-label, two-part, multicenter study to assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of BDTX-189, in adult patients with advanced solid tumors who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. Part A is a Phase 1, first-in-human, open-label dose escalation study, comprised of initial single-patient, accelerated titration cohorts followed by multiple-patient cohorts utilizing a Bayesian design. Part A is designed to determine the recommended Phase 2 dose and schedule in up to 100 patients with allosteric human epidermal growth factor receptor 2 (HER2) or HER3 mutation; epidermal growth factor receptor (EGFR) or HER2 exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or, EGFR exon 19 deletion or L858R mutation. Part B is a Phase 2, open-label, multicenter basket study designed to determine antitumor activity and safety in adult patients with solid tumors that have an allosteric HER2 mutation or EGFR or HER2 exon 20 insertion mutations using next-generation sequencing. This part will utilize a Simon 2-stage design and enroll up to 100 patients in four cohorts: 1) non-small cell lung cancer with EGFR or HER2 exon 20 insertion mutations; 2) breast cancer with an allosteric ErbB mutation; 3) solid tumors (except breast) with S310F/Y mutation; and, 4) other tumors harboring allosteric ErbB mutations not included in cohorts 1-3.

About BDTX-189

BDTX-189 is an orally available, irreversible small molecule inhibitor that is designed to block the function of family of oncogenic proteins defined by driver mutations across a range of tumor types, and which affect both of the epidermal growth factor receptor (EGFR) and the tyrosine-protein kinase, ErbB-2, or human epidermal growth factor receptor 2 (HER2). BDTX-189 is designed as a MasterKey inhibitor targeting a family of previously undrugged and functionally similar mutations in a tumor-agnostic manner. These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain Exon 20 insertions, and additional activating oncogenic drivers of ErbB. The ErbB receptors are a group of receptor tyrosine kinases involved in key cellular functions, including cell growth and survival. BDTX-189 is also designed to spare normal, or wild-type, EGFR, which we believe has the potential to improve upon the toxicity profiles of current ErbB kinase inhibitors. Currently, there are no medicines approved by the FDA to target all of these oncogenic mutations with a single therapy.

BDTX-189 is currently being evaluated in a Phase 1/2 clinical trial (MasterKey-01) in adult patients with advanced solid tumors with at least one MasterKey mutation who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. In July 2020, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric HER2 mutation or an EGFR or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options.

On November 10, 2020 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported pipeline updates, recent business highlights and third quarter 2020 financial results (Press release, Beam Therapeutics, NOV 10, 2020, View Source [SID1234570443]).

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"2020 has been a year of significant progress for Beam," said John Evans, chief executive officer of Beam. "Since the start of the year, we’ve named three development candidates from our portfolio, now including BEAM-201, our multiplex editing program for the treatment of T-cell acute lymphoblastic leukemia. We are also pleased to report that we’re on track to submit our first IND in the second half of 2021, with BEAM-101 for the treatment of sickle cell disease. The continued advancement of our pipeline is a testament to both the strength and breadth of our base editing platform and our exceptional team. Combined with the capital we’ve added to our balance sheet, we are well positioned to continue our strategy of advancing multiple programs to the clinic in parallel, in the hope of providing much-needed new treatment options for patients with serious diseases."

Base Editing Progress

First CAR-T Base Editing Development Candidate, BEAM-201, Named for Treatment of T-ALL; Data Presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020): Beam is advancing BEAM-201, a potent and specific anti-CD7 CAR-T multiplex editing program for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL), a severe disease affecting children and adults with five-year overall survival of less than 25%. BEAM-201 is produced using a GMP-compliant, clinical-scale process in which T-cells derived from healthy donors are simultaneously base edited at four genomic loci then transduced with a lentivirus coding for an anti-CD7 CAR. The resulting cells are universally-compatible, allogeneic ("off the shelf") CD7-targeting CAR-T cells resistant to both fratricide and immunosuppression. Preclinical data from this approach were reported in a poster as part of SITC (Free SITC Whitepaper) 2020, which is being held virtually from November 9-14, 2020. Editing with BEAM-201 led to potent, dose-dependent tumor control in vitro and in an in vivo xenograft mouse model. Details of the presentation are as follows:
Title: Highly Efficient Multiplexed Base Editing Enables the Development of Investigational Universal CD7-targeting CAR-T Cells to Treat T-ALL
Publication Number: 111
Category: Cellular Therapies
Upcoming Base Editing Data Presentations

First Data Highlighting Base Editing Program for Glycogen Storage Disease Type Ia to be Presented at American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting Digital Experience: Beam will present the first data highlighting its novel base-editing strategy for correcting disease-causing mutations underlying Glycogen Storage Disease Type Ia (GSDIa) during a poster session at AASLD’s The Liver Meeting Digital Experience, which is being held virtually November 13-16, 2020. Details of the presentation are as follows:
Title: Base-Editing as a Therapeutic Approach for the Direct Correction of Disease-Causing Mutations Underlying Glycogen Storage Disease Type Ia
Publication Number: 0589
Session Title: Genomics and Precision Medicine
Beam will also report data during an oral presentation at AASLD from its Alpha-1 Antitrypsin Deficiency (Alpha-1) program. Details of the presentation are as follows:

Title: Evaluation of Adenine Base Editing as a Potential Treatment for Alpha-1 Antitrypsin Deficiency
Publication Number: 0032
Session Title: Parallel 3: Metabolic and Genetic Diseases
Session Broadcast Date and Time: Saturday, November 14, 2020, 2:00 p.m. ET
Updated Data from Novel Sickle Cell Disease Approaches to be Presented at 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2020): Beam is pursuing two differentiated base editing approaches to treat hemoglobinopathies, BEAM-101 and BEAM-102, and will present updated preclinical data from these two complementary editing programs during poster sessions at ASH (Free ASH Whitepaper) 2020, being held virtually December 5-8, 2020. Details of the presentations are as follows:
Title: Adenine Base Editing of the Sickle Allele in CD34+ Hematopoietic Stem and Progenitor Cells Eliminates Hemoglobin S
Session: 801. Gene Editing, Therapy and Transfer: Poster I
Date: Saturday, December 5, 2020
Publication Number: 1543
Title: Adenine Base Editing of Gamma Globin Gene Promoters Shows No Detectable Off-Target RNA or DNA Editing
Session: 801. Gene Editing, Therapy and Transfer: Poster I
Date: Saturday, December 5, 2020
Publication Number: 1545
Recent Business Highlights

Successful $135 Million Follow-on Offering Completed: In October 2020, Beam sold 5,000,000 shares of common stock at a public offering price of $23.50 per share. Underwriters exercised in full their option to purchase up to an additional 750,000 shares of common stock at the public offering price, less the underwriting discounts and commissions. The gross proceeds of the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Beam, were approximately $135.1 million. The net proceeds of the offering were $126.6 million.
Leadership Update – Courtney Wallace Promoted to Chief Business Officer: In November 2020, Beam promoted Courtney Wallace to chief business officer. Ms. Wallace previously served as senior vice president, head of business development and strategy at Beam. Ms. Wallace has served as Beam’s head of corporate strategy and business development since 2018.
Upcoming Investor Conference Presentation

John Evans, chief executive officer, will participate in a fireside chat during the Jefferies Virtual London Healthcare Conference on Thursday, November 19, 2020 at 4:25 p.m. GMT/11:25 a.m. ET.

The live webcast will be available in the investor section of the company’s website at www.beamtx.com. The webcast will be archived for 60 days following the presentation.

Third Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $202.2 million as of September 30, 2020. This cash balance does not include the proceeds of the October 2020 offering.
Research & Development (R&D) Expenses: R&D expenses were $29.8 million for the quarter ended September 30, 2020, compared to $12.5 million for the quarter ended September 30, 2019.
General & Administrative (G&A) Expenses: G&A expenses were $7.5 million for the quarter ended September 30, 2020, compared to $5.5 million for the quarter ended September 30, 2019.
Net Loss: Net loss attributable to common stockholders was $34.5 million, or $0.69 per share, for the quarter ended September 30, 2020, compared to $22.3 million, or $3.31 per share, for the quarter ended September 30, 2019.

On November 10, 2020 Avidity Biosciences, Inc. (Nasdaq: RNA), a biopharmaceutical company pioneering a new class of oligonucleotide-based therapies called Antibody Oligonucleotide Conjugates (AOCs), reported financial results for the quarter ended September 30, 2020 and highlighted recent corporate progress (Press release, Avidity Biosciences, NOV 10, 2020, View Source [SID1234570442]).

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"During the third quarter, we continued to invest in all aspects of our business and advanced our muscle-disease programs toward the clinic," said Sarah Boyce, President and Chief Executive Officer. "In the near term, we are focused on preparing for the initiation of our first clinical study with AOC 1001 in adults with myotonic dystrophy type 1. We are also advancing our research efforts in new tissues and cell types beyond muscle that we believe we can effectively target with AOCs to create new therapies designed to improve the lives of patients with serious diseases."

"As we prepare for clinical development with AOC 1001, we maintain a strong financial position with $341 million in cash at quarter-end," said Mike MacLean, Chief Financial Officer. "With our current financial resources, we are well-positioned to meet our goals and advance multiple AOC programs into the clinic in the next two years."

Third Quarter 2020 and Recent Corporate Highlights

Presented at Key Scientific Meetings. Avidity presented at several key virtual scientific meetings, including TIDES USA 2020, the 16th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) 2020, the Next Generation Protein Therapeutics and Bioconjugates Summit 2020, and TIDES Europe 2020. In early December 2020, the company plans to present an overview of its AOC technology and preclinical data at the 3rd Annual Neuromuscular Drug Development Summit.
Entered into Collaboration to Study the Natural History of DM1 to Support Lead Program AOC 1001. Avidity entered into a collaboration supporting END-DM1 (Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1), a natural history study to advance the understanding of disease progression in patients with myotonic dystrophy type 1 (DM1). This new collaboration supports Avidity’s lead program, AOC 1001, in development for the treatment of DM1. END-DM1 is a non-interventional study designed and run by the Myotonic Dystrophy Clinical Research Network (DMCRN), a network of medical centers. DMCRNaims to support future clinical trials of potential therapies for DM1 through the generation of evidence around endpoint measures and testing methods.
Appointed Key New Hires to Leadership Positions. Avidity welcomed three new team members into leadership positions: Teresa McCarthy, Chief Human Resources Officer, Kelly DiTrapani, Vice President of Medical Affairs, and Monica Zepeda, Vice President of Program and Alliance Management. Avidity strives to achieve a strong diversity climate and celebrates its newest female executives.
Financial Results

Cash and Cash Equivalents: Cash and cash equivalents totaled $341.1 million as of September 30, 2020, which includes net proceeds of $274.1 million from the company’s IPO in June 2020, compared to cash and cash equivalents of $94.6 million as of December 31, 2019.
Collaboration Revenue: Collaboration revenue, including reimbursable expenses, was $1.7 million for the third quarter of 2020 compared with $0.7 million for the third quarter of 2019, and $4.6 million for the first nine months of 2020 compared with $0.9 million for the first nine months of 2019.
Research and Development (R&D) Expenses: R&D expenses, including external and internal costs associated with research activities, primarily relate to the progression of the company’s research on AOC 1001 and other programs. These expenses were $9.5 million for the third quarter of 2020 compared with $5.1 million for the third quarter of 2019, and $24.0 million for the first nine months of 2020 compared with $8.9 million for the first nine months of 2019. The increases were primarily driven by the advancement of AOC 1001, as well as other programs.
General and Administrative (G&A) Expenses: G&A expenses primarily consist of employee-related expenses, professional fees, insurance costs, and patent filing and maintenance fees. These expenses were $3.8 million for the third quarter of 2020 compared with $0.8 million for the third quarter of 2019, and $8.6 million for the first nine months of 2020 compared with $3.3 million for the first nine months of 2019. The increases were primarily due to higher personnel costs (including noncash stock-based compensation), professional fees and insurance costs related to being a public company, as well as higher patent filing fees.

On November 10, 2020 Aura Biosciences, a clinical-stage biopharmaceutical company developing a novel class of tumor targeted therapies for initial application in primary tumors such as choroidal melanoma, reported that an abstract has been selected as a late breaking presentation as part of the Retina Subspecialty Day at the upcoming American Academy of Ophthalmology (AAO) 2020 Virtual Annual Meeting, taking place November 14-17, 2020 (Press release, Aura Biosciences, NOV 10, 2020, View Source [SID1234570440]). The abstract details results from the ongoing intravitreal administration Phase 1b/2 clinical study and suprachoroidal administration Phase 2 clinical study evaluating AU-011 in patients with choroidal melanoma.

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This late-breaking presentation will be given by Carol L. Shields, M.D., Director, Ocular Oncology Service at Wills Eye Hospital, and Professor of Ophthalmology at Thomas Jefferson University. Other key presentations will be given by Brian P. Marr, M.D., Director, Division of Ophthalmic Oncology, New York-Presbyterian/Columbia Medical Center and Ivana K. Kim, M.D., Co-Director, Ocular Melanoma Center, Massachusetts Eye and Ear, and Associate Professor of Ophthalmology, Harvard Medical School, and will also highlight updated clinical data from Aura’s ongoing Phase 1b/2 AU-011 clinical trial, and the overall development plan including the ongoing Phase 2 study evaluating suprachoroidal administration of AU-011, also in patients with primary choroidal melanoma.

Details for the AAO 2020 presentations are as follows:

Late breaker title: AU-011, a Targeted Therapy for Primary Treatment of Choroidal Melanoma (CM) via Intravitreal (IVT) and Suprachoroidal (SC) Administration

Presenter: Carol S. Shields, MD, Wills Eye Hospital

Session: RET10V

Date and time: Friday, November 13, 2020 from 3:15 – 3:20 PM PT

Location: Virtual Live Meeting Broadcast

Title: AU-011 for Choroidal Melanoma: Trial Update

Presenter: Brian P. Marr, MD, New York-Presbyterian/Columbia medical Center

Session: PTH05V

Date and time: Friday, November 13, 2020 from 4:02 – 4:07 PM PT

Location: Virtual Live Meeting Broadcast

Title: Update from an Ongoing Phase 1b/2 Open-label Trial with Intravitreal (IVT) AU-011 for Choroidal Melanoma (CM) and Further Development Plan

Presenter: Ivana K. Kim, MD, Massachusetts Eye and Ear

Session: PA034

Date and time: Available on demand Nov 14-15, 2020

Location: Virtual Meeting Live Broadcast

About Choroidal Melanoma

Choroidal melanoma is a rare and life-threatening type of eye cancer. It is the most common primary intraocular cancer in adults and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts, and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes in approximately 50 percent of patients with liver involvement in 80-90% of cases and, unfortunately, metastatic disease is universally fatal (source: OMF). There is a very high unmet need for a new vision sparing targeted therapy that could enable early treatment intervention for this life-threatening rare disease given the lack of approved therapies, and the comorbidities of radioactive treatment options.

About AU-011 (belzupacap sarotalocan)

AU-011 is a first-in-class targeted therapy in development for the treatment of primary choroidal melanoma. The therapy consists of proprietary viral-like particle bioconjugates (VPB) that are activated with an ophthalmic laser. The VPBs bind selectively to unique receptors on cancer cells in the eye and are derived from technology originally pioneered by Dr. John Schiller of the Center for Cancer Research at the National Cancer Institute (NCI), recipient of the 2017 Lasker-DeBakey Award. Upon activation with an ophthalmic laser, the drug rapidly and specifically disrupts the cell membrane of malignant tumor cells while sparing key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted orphan drug and fast track designations by the U.S. Food and Drug Administration and is currently in clinical development.

About Suprachoroidal Administration

In addition to intravitreal administration, Aura is also investigating AU-011 using the suprachoroidal (SC) route of administration. Aura believes that delivering AU-011 into the suprachoroidal space (SCS) within the eye, has the potential to offer certain advantages over intravitreal injection, including higher bioavailability at the tumor site and reduced exposure of non-targeted tissues, which may lead to an improved therapeutic index for AU-011. Collectively, these features could allow for the treatment of a wider range of tumor sizes, and, therefore, a larger number of patients. The Company is partnered with Clearside Biomedical for use of Clearside’s SCS Microinjector for administration of AU-011 into the SCS. In preclinical research presented as part of the ARVO 2020 virtual program, AU-011 showed excellent distribution in the SCS, complete necrosis of tumors following laser activation in an animal model of choroidal melanoma and no clinical signs of anterior segment or posterior segment inflammation.

On November 10, 2020 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated agents that target the underlying mechanisms of cancer, reported financial results and a corporate update for the three months ended September 30, 2020 (Press release, Aptose Biosciences, NOV 10, 2020, View Source [SID1234570439]).

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The net loss for the quarter ended September 30, 2020 was $13.3 million ($0.15 per share) compared with $6.8 million ($0.12 per share) for the quarter ended September 30, 2019. Total cash and cash equivalents and investments as of September 30, 2020 were $132.7 million. Based on current operations, we expect that cash on hand provides the Company with sufficient resources to fund all planned operations including research and development into 2023.

"With our recently initiated Phase 1 a/b trial of CG-806 in patients with relapsed or refractory (R/R) acute myeloid leukemia, we now have three clinical trials under way – two studies with our FLT3 and BTK kinase inhibitor CG-806 and one with our MYC inhibitor APTO-253," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "Enrollment of AML patients has been brisk at the 450mg BID dose level and clinical site investigators are hopeful about the potential for CG-806 as a therapeutic option in relapsed or refractory AML. In our B-cell malignancy clinical trial, we are beginning to observe nodal reductions in the deep R/R-CLL and SLL patients and are treating patients at dose level 5 (750 mg BID), which gives us optimism that clinical responses may emerge over time. We look forward to sharing more details from our CG-806 and APTO-253 programs with you at a corporate update just a few weeks from now during ASH (Free ASH Whitepaper)."

Key Corporate Highlights

CG-806 Phase 1 a/b Clinical Study in AML – In October, Aptose announced dosing of the first patient with R/R acute myeloid leukemia (AML) in a Phase 1 a/b clinical study with CG-806, the Company’s oral kinase inhibitor that potently inhibits the wildtype and mutant forms of FLT3 and BTK, and suppresses select clusters of kinases that drive oncogenic signaling pathways. The Phase 1 a/b trial is a multicenter open-label, dose escalation study of safety, pharmacodynamics, and pharmacokinetics of CG-806 in ascending cohorts (3+3 design) to determine the maximum tolerated dose or recommended dose in patients with relapsed or refractory AML. The investigational drug is the only known clinical agent that potently inhibits both FLT3 and BTK, giving it broad therapeutic potential across the spectrum of lymphoid and myeloid hematologic malignancies. Currently, 5 U.S. sites are open for screening and enrolling patients for the study, and more information is available at www.clinicaltrials.gov (NCT04477291).

CG-806 Phase 1 a/b B-cell Malignancy Clinical Study – Separate from the AML trial, Aptose is treating patients at the fifth dose level of 750 mg BID in its Phase 1 a/b dose escalation study with CG-806 in patients with R/R B-cell malignancies, including chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphomas (NHL), who have failed or are intolerant to current therapies. At the 750mg dose Aptose is focusing exclusively on enrolling CLL patients, where on-target activity has been observed, including inhibition of multiple oncogenic driver kinases, lymphocytosis, classically ascribed as a consequence of inhibiting BTK, as well as nodal reductions. Currently, 29 U.S. sites are open for screening and enrolling patients for the study, and more information is available at www.clinicaltrials.gov (NCT03893682).

APTO-253 Phase 1b Clinical Study in R/R AML and MDS – Aptose has completed the 28-day dosing in the first four dose cohorts of the Phase 1b clinical study of APTO-253 in patients with relapsed or refractory AML or high-risk MDS. The Company has enrolled three patients at dose level five (150 mg/m2), which represents a 50% increase over dose level four. APTO-253 is the only known clinical-stage molecule that can directly target and inhibit expression of the MYC oncogene, shown to reprogram survival signaling pathways and contribute to drug resistance in many malignancies, including AML and B cell malignancies. In the ongoing Phase 1b trial, 253 continues to be well tolerated with no evidence of drug-related adverse events, including no observed myelosuppression. More information is available at www.clinicaltrials.gov (NCT02267863).

Upcoming Presentations at ASH (Free ASH Whitepaper) – Last week, Aptose announced that early clinical data, along with certain preclinical data, for CG-806, an oral, first-in-class FLT3 and BTK cluster selective kinase inhibitor, and early clinical data for APTO-253, a first-in-class small molecule MYC inhibitor, will be presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held virtually Saturday, December 5 – Monday, December 7, 2020. The abstracts accepted for presentation can be viewed online at the ASH (Free ASH Whitepaper) conference website. Note that the poster presentations will include additional data not found in the abstracts.

In addition, Aptose is planning to hold a corporate update during ASH (Free ASH Whitepaper) to review the most current clinical data for each of the ongoing trials. More details to follow.

RESULTS OF OPERATIONS

A summary of the results of operations for the three-month and nine-month periods ended September 30, 2020 and 2019 is presented below:

The net loss for the three-month period ended September 30, 2020 increased by $6.4 million to $13.2 million as compared with $6.8 million for the comparable period in 2019, primarily as a result of an increase of $4.4 million in stock-based compensation in the current period, a combined increase in costs for our CG-806 development program and related labor costs of approximately $2.5 million and offset by lower costs of approximately $721 thousand on our APTO-253 program. There was also an increase in cash-based general and administrative expenses of $108 thousand and a decrease in net finance income of $138 thousand in the current period compared to the comparative period, mostly as a result of lower yields on investments held during the three-month period ended September 30, 2020.

The net loss for the nine-month period ended September 30, 2020 increased by $22.0 million to $40.5 million as compared with $18.6 million for the comparable period in 2019, primarily as a result of an increase of $15.3 million in stock-based compensation in the current period, a combined increase in program costs and related labor costs of approximately $7.1 million on our CG-806 development program and higher cash-based general and administrative expenses of approximately $492 thousand. These expenses were partially offset by lower costs of $836 thousand on our APTO-253 development programs.

Research and Development
The research and development expenses for the three-month and nine-month periods ended September 30, 2020 and 2019 were as follows:

Research and development expenses increased by $2.8 million to $7.5 million for the three-month period ended September 30, 2020 as compared with $4.8 million for the comparative period in 2019. Changes to the components of our research and development expenses presented in the table above are primarily as a result of the following events:

Program costs for CG-806 increased by approximately $2.1 million, mostly as a result of higher manufacturing costs, including costs to scale up manufacturing and research costs associated with optimizing the formulation, higher costs associated with the CG-806 Phase 1a/b trial and the costs associated the CG-806 AML trial.

Program costs for APTO-253 decreased by approximately $721 thousand, mostly as a result of lower manufacturing costs and lower clinical trial costs related to the APTO-253 Phase 1b trial.

Personnel-related expenses increased by $398 thousand, mostly related to new positions hired since the second quarter of 2019 to support the CG-806 Phase 1a/b and APTO-253 Phase 1b clinical trials and the CG-806 AML Phase 1 clinical trial.

Stock-based compensation increased by approximately $1.0 million in the three months ended September 30, 2020, compared with the three months ended September 30, 2019, mostly related to an increase in the number of options granted during the nine months ended September 30, 2020 and a higher grant date fair value of options as compared with the nine months ended September 30, 2019, and a higher rate of forfeitures in the comparative period.
Research and development expenses increased by $8.7 million to $20.3 million for the nine-month period ended September 30, 2020 as compared with $11.6 million for the comparative period in 2019 for the same reasons as described above for the three-month period ended September 30, 2020.

Program costs for CG-806 increased by approximately $5.7 million, mostly as a result of higher manufacturing costs, including costs to scale up manufacturing and research costs associated with optimizing the formulation, higher costs associated with the CG-806 Phase 1a/b trial and the costs associated with the CG-806 AML trial.

Program costs for APTO-253 decreased by approximately $836 thousand, mostly as a result of lower manufacturing costs and lower clinical trial costs related to the APTO-253 Phase 1b trial.

Personnel-related expenses increased by $1.4 million, mostly related to new positions hired since the second quarter of 2019 to support the CG-806 Phase 1a/b and APTO-253 Phase 1b clinical trials and the CG-806 AML Phase 1 clinical trial.

Stock-based compensation increased by approximately $2.5 million in the three months ended September 30, 2020, compared with the three months ended September 30, 2019, mostly related to an increase in the number of options granted during the nine months ended September 30, 2020 and a higher grant date fair value of options as compared with the nine months ended September 30, 2019, and a higher rate of forfeitures in the comparative period in 2019.
General and Administrative
The general and administrative expenses for the three-month and nine-month periods ending September 30, 2020 and 2019 were as follows:

General and administrative expenses for the three-month period ended September 30, 2020 were $5.8 million as compared with $2.3 million for the comparative period in 2019, an increase of approximately $3.5 million. The increase was primarily as a result of the following:

General and administrative expenses, other than share-based compensation and depreciation of equipment, increased by approximately $108 thousand in the three months ended September 30, 2020, primarily as a result of higher personnel related costs, higher insurance costs and higher office administrative costs offset by lower professional fees and lower travel expenses.

Stock-based compensation increased by approximately $3.4 million in the three months ended September 30, 2020, compared with the three months ended September 30, 2019, mostly related to an increase in the number of options granted during the nine-month period ended September 30, 2020, and a higher grant date fair value of options as compared with September 30, 2019.
General and administrative expenses for the nine-month period ended September 30, 2020 were $20.7 million as compared with $7.4 million for the comparative period in 2019, an increase of approximately $13.3 million. The increase was primarily as a result of the following:

General and administrative expenses, other than stock-based compensation and depreciation of equipment, increased by approximately $492 thousand in the nine months ended September 30, 2020 primarily as a result of higher personnel related costs, higher insurance costs and higher office administrative costs and offset by lower financing costs and lower travel expenses.

Stock-based compensation increased by approximately $12.8 million in the nine months ended September 30, 2020, compared with the nine months ended September 30, 2019 mostly related to an increase in the number of restricted share units and options granted during the nine-month period ended September 30, 2020, and a higher grant date fair value of options as compared with September 30, 2019.
COVID-19 did not have a significant impact on our results of operations for the quarter ended September 30, 2020. We have not experienced and do not foresee material delays to the enrollment of patients or timelines for the CG-806 Phase 1a/b trial due to the variety of clinical sites that we have actively recruited for this trial. Similarly, we do not expect our enrollment of the CG-806 AML trial to be negatively impacted by COVID-19 as we plan to use a variety of clinical sites for this trial as well. APTO-253, which is administered intravenously, requires the need for hospital / clinical site resources to assist and monitor patients during each infusion and, based on the current conditions caused by COVID-19, future enrollment of patients on this trial is likely to be negatively impacted. As of the date of this report, we have not experienced material delays in the manufacturing of CG-806 or APTO-253 related to COVID-19. Should our manufacturers be required to shut down their facilities due to COVID-19 for an extended period of time, our trials may be negatively impacted.

Conference Call and Webcast

Aptose will host a conference call to discuss results for the quarter ended September 30, 2020 today, Tuesday, November 10, 2020 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/toll number) and using conference ID #5539639. 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 (toll free number) and 1-404-537-3406 (international/toll number), using the conference ID # 5539639.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended September 30, 2020 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.