On May 9, 2022 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral kinase inhibitors to treat hematologic malignancies, reported financial results for the three months ended March 31, 2022 and provided a corporate update (Press release, Aptose Biosciences, MAY 9, 2022, View Source [SID1234613931]).

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The net loss for the quarter ended March 31, 2022 was $11.5 million ($0.12 per share) compared with $16.2 million ($0.18 per share) for the quarter ended March 31, 2021. Total cash and cash equivalents and investments as of March 31, 2022 were $69.5 million. Based on current operations, Aptose expects that cash on hand and available capital provide the Company with sufficient resources to fund all planned Company operations including research and development into the fourth quarter of 2023.

"Aptose has two meaningful clinical-stage kinome inhibitors in HM43239 and luxeptinib, and we continue to advance their development in distinct patient populations," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "To date, both have demonstrated clear activity and have been well-tolerated. As we define the next steps in the development program with our lead compound HM43239, we are encouraged by the clinical remissions we are seeing in AML patients, particularly in those with highly adverse mutations that typically are difficult to treat but respond to HM43239. We look forward to reporting all available data on our programs at an upcoming corporate event."

Key Corporate Highlights

Aptose Receives Fast Track Designation for HM43239 – The U.S. Food and Drug Administration (FDA) granted Fast Track designation to HM43239 (239), an oral, myeloid kinome inhibitor, for the treatment of patients with relapsed, refractory (R/R) acute myeloid leukemia (AML) who have FLT3 mutations. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.The purpose is to get important new drugs to patients earlier.

HM43239 Expansion at 160 mg in Diverse AML Patient Population – HM43239, an oral, myeloid kinome inhibitor in an international Phase 1/2 trial in patients with relapsed or refractory acute myeloid leukemia (AML), thus far has delivered six composite complete remissions (CR) and a PR at the 80 mg and 120 mg doses. Aptose is now expanding at the 160 mg dose level, with the goal of understanding the breadth of activity of 239 in diverse mutations and identifying the best efficacious and safe doses to treat relapsed and refractory AML. HM43239 thus far has demonstrated a favorable safety profile with no DLTs and no drug discontinuations from drug related toxicity at doses up to 160 mg per day.

Headway with Luxeptinib "G3" Formulation in Patients – Luxeptinib , a dual lymphoid and myeloid kinome inhibitor, currently is being evaluated in a Phase 1 a/b study in patients with relapsed or refractory AML and higher risk MDS, and in a separate Phase 1 a/b study in patients with relapsed or refractory B-cell malignancies. Aptose has made significant progress with the clinical evaluation of a new formulation of luxeptinib (Lux), that may enable greater exposures across patients. In the ongoing studies in AML and B-cell malignancies, a dose of the G3 formulation has been safely administered to three patients at the 50 mg dose level and is now being dosed at the 100 mg dose level. After patients receive the single G3 dose, samples are collected for PK evaluation and patients then go onto the original formulation of Lux for comparison.

Aptose Appoints Chief Commercial Officer – Aptose recently appointed Dr. Philippe Ledru to the position of Chief Commercial Officer, responsible for providing executive leadership and vision for commercial development and marketing strategies for the future commercial launches of HM43239 and luxeptinib and to consolidate responsibilities over business development and licensing. Dr. Ledru most recently served as Associate Vice President and Head of Oncology New Products at Merck & Co., over 25 assets from discovery to mid-stage clinical development, across major solid tumors and hematological malignancies At Merck, he also provided leadership on all licensing and M&A activities, including the Peloton Therapeutics and Arqule acquisitions in 2019. Earlier, at Novartis, he had early commercial development and global marketing responsibilities for several new compounds, including FLT3 inhibitor midostaurin, and at Novartis Oncologie he helped lead launches of several oncology products, including imatinib (Gleevec).

RESULTS OF OPERATIONS

A summary of the results of operations for the three-month periods ended March 31, 2022 and 2021 is presented below:

The net loss for the three-month period ended March 31, 2022, decreased by $4.7 million to $11.5 million as compared with $16.2 million for the comparable period in 2021. Components of the net loss are presented below:

Research and Development

Research and development expenses consist primarily of costs incurred related to the research and development of our product candidates. Costs include the following:

External research and development expenses incurred under agreements with third parties, such as CROs, consultants, members of our scientific advisory boards, external labs and CMOs; and

Employee-related expenses, including salaries, benefits, travel, and stock-based compensation for personnel directly supporting our clinical trials and manufacturing, and development activities.
We have ongoing Phase 1 clinical trials for our product candidates HM43239 and Luxeptinib. HM43239 was licensed into Aptose in Q4, 2021 and we have assumed sponsorship, and the related costs, of the HM43239 study effective January 1, 2022. In Q4, 2021, we discontinued the APTO-253 program and are exploring strategic alternatives for this compound.

We expect our research and development expenses to be higher for the foreseeable future as we continue to advance HM43239 and luxeptinib into larger clinical trials.

The research and development expenses for the three-month periods ended March 31, 2022, and 2021 were as follows:

Research and development expenses decreased by $835 thousand to $7.4 million for the three-month period ended March 31, 2022 as compared with $8.2 million for the comparative period in 2021. 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 HM43239 increased by approximately $1.2 million as the Company in-licensed the development rights of HM43239 in the fourth quarter of 2021 and assumed sponsorship, and the related costs, of the study effective January 1, 2022.

Program costs for luxeptinib decreased by approximately $1.1 million, primarily due to lower manufacturing costs as a result of the current formulation requiring less API than the prior formulation and also from lower clinical trial costs, mostly related to fewer contractors needed to support the trials.

Program costs for APTO-253 decreased by approximately $1.0 million, due to the Company’s decision on December 20, 2021 to discontinue further clinical development of APTO-253.

Personnel-related expenses increased by $546 thousand, mostly related to new positions hired in 2021 to support our clinical trials and manufacturing activities.

Stock-based compensation decreased by approximately $432 thousand in the three months ended March 31, 2022, compared with the three months ended March 31, 2021, primarily due to lower grant date fair value of options which were granted in the current period.
General and Administrative

General and administrative expenses consist primarily of salaries, benefits and travel, including stock-based compensation for our executive, finance, business development, human resource, and support functions. Other general and administrative expenses are professional fees for auditing, and legal services, investor relations and other consultants, insurance and facility related expenses.

We expect that our general and administrative expenses will increase for the foreseeable future as we incur additional costs to support the expansion of our pipeline of activities. We also expect our intellectual property related legal expenses to increase as our intellectual property portfolio expands.

The general and administrative expenses for the three-month periods ended March 31, 2022 and 2021 were as follows:

General and administrative expenses for the three-month period ended March 31, 2022 were $4.1 million as compared with $8.0 million for the comparative period in 2021, a decrease of approximately $3.9 million. The decrease was primarily as a result of the following:

General and administrative expenses, other than stock-based compensation and depreciation of equipment, decreased by approximately $204 thousand in the three months ended March 31, 2022 primarily as a result lower professional fees.

Stock-based compensation decreased by approximately $3.7 million in the three months ended March 31, 2022, compared with the three months ended March 31, 2021, primarily due to lower grant date fair value of options which were granted in the current period, and additional compensation recognized in the comparative period for modifications made to then vested and unvested stock options for one officer, as part of a separation and release agreement.
COVID-19 did not have a significant impact on our results of operations for the three-month period ended March 31, 2022. We have not experienced and do not foresee material delays to the enrollment of patients or timelines for the HM43239 Phase 1/2 trial or the luxeptinib Phase 1a/b trials due to the variety of clinical sites that we have actively recruited for these trials. As of the date of this report, we have not experienced material delays in the manufacturing of HM43239 or luxeptinib 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 March 31, 2022 today, Monday, May 9, 2022 at 5:00 PM ET. Participants can access the conference call by dialing 1-866-374-5140 (North American toll-free number) and 1-404-400-0571 (international/toll number) and using conference ID 38238231#. 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 will be available on the Company’s website for 30 days.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended March 31, 2021 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

On May 9, 2022 Ascendis Pharma A/S (Nasdaq: ASND) reported that the company is scheduled to attend the BofA Securities 2022 Healthcare Conference (Press release, Ascendis Pharma, MAY 9, 2022, View Source [SID1234613947]). Company executives will participate in a fireside chat hosted by BofA on Thursday, May 12.

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A live webcast of the event will be available on the Investors and News section of the Ascendis Pharma website at www.ascendispharma.com. A webcast replay will be available on this website shortly after conclusion of the event for 30 days.

On May 9, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported that the U.S. Food and Drug Administration (FDA) has cleared Elpiscience’s ES014 Investigational New Drug (IND) Application to initiate a Phase 1 clinical study for patients with advanced solid tumors (Press release, Elpiscience, MAY 9, 2022, View Source [SID1234613964]). ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody (bsAb) that simultaneously targets the CD39-adenosine and TGF-β pathways, two major immunosuppressive mechanisms in the tumor microenvironment (TME).

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"We are delighted that our IND for ES014 was cleared by FDA," said Steve Chin, Chief Medical Officer of Elpiscience. "ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody. In preclinical studies, ES014 demonstrated significant anti-tumor activity in a PD-1 resistant in vivo efficacy model. We look forward to starting the Phase 1 study soon."

Solid tumors frequently express TGF-β, which suppresses T cell activation and induces CD39 expression, the rate-limiting enzyme in the ATP-adenosine pathway​. The anti-CD39 target is designed to selectively direct ES014 to the TME where the anti-TGF-β activity promotes effector T cell function and immune activation, while avoiding or minimizing systemic immunotoxicity. ES014’s anti-CD39 activity further aims to reverse TME immunosuppression by reducing suppressive adenosine, while maintaining high levels of immune-stimulatory extracellular ATP. The combined removal of immune suppression and immune stimulating effects of ES014 were recently demonstrated in a PD-1 antibody non-responsive in vivo animal model where tumor growth was significantly inhibited after treatment.

On May 9, 2022 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the first quarter of 2022 and provided business updates (Press release, Caribou Biosciences, MAY 9, 2022, View Source [SID1234614000]).

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"Building on the momentum and significant achievements of 2021, we focused on execution and the advancement of our pipeline of genome-edited allogeneic CAR-T and CAR-NK cell therapies in the first quarter of 2022," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "We continue to enroll patients in our ANTLER Phase 1 clinical trial of CB-010 and we are slated to share initial data from patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) at EHA (Free EHA Whitepaper) next month. This year, we plan to submit an IND application for CB-011 to rapidly advance our second CAR-T program into the clinic, and we expect to share target selection for CB-020, the first solid tumor-targeted program from our CAR-NK platform."

Recent Business Highlights

Pipeline

CB-010: In April 2022, an abstract with initial clinical data from the ANTLER Phase 1 trial of CB-010 in adults with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) was accepted at EHA (Free EHA Whitepaper), being held in Vienna, Austria, June 9-17, 2022.
Caribou’s lead product candidate, CB-010, is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology to insert a CD19-specific CAR into the TRAC gene and knock out PD-1 to boost the persistence of antitumor activity. More information can be found at www.clinicaltrials.gov (NCT04637763).
Caribou continues to enroll patients in ANTLER.
CB-011: Caribou is conducting IND-enabling studies to support an IND application submission in H2 2022 in patients with relapsed or refractory multiple myeloma (r/r MM).
In April 2022, promising preclinical data supporting the development of CB-011 were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.
CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA technology to insert a BCMA-specific CAR into the TRAC gene and armor the cells with an immune cloaking strategy that includes a knockout of the endogenous B2M gene and site-specific insertion of a B2M–HLA-E fusion transgene into the B2M gene. This immune cloaking strategy is designed to blunt both T- and NK-mediated immune cell rejection, enabling more durable antitumor activity.
Corporate

In January 2022, Caribou appointed Syed Rizvi, M.D., as chief medical officer. Dr. Rizvi has more than two decades of experience in all stages of drug development, from clinical strategy and execution through regulatory submissions to support approval and commercialization of several cancer treatments, including three approved autologous CAR-T cell therapies ABECMA, BREYANZI, and CARVYKTI. Prior to joining Caribou, Dr. Rizvi served as chief medical officer of Chimeric Therapeutics and worked for Legend Biotech, Celgene Corporation (now Bristol Myers Squibb), Novartis, Merck, and Genta, Inc.
In January 2022, Zili An, M.D., joined Caribou as vice president of pharmacology. He brings over 20 years of drug development experience in multiple cancer therapeutic modalities, including CAR-T cell therapies.
Anticipated Milestones for 2022 and Beyond

CB-010: Caribou is scheduled to share initial data from its ongoing ANTLER Phase 1 trial for CB-010, an anti-CD19 CAR-T cell therapy for r/r B- NHL, at EHA (Free EHA Whitepaper) in June 2022.
CB-011: Caribou expects to submit an IND application for CB-011, an anti-BCMA CAR-T cell therapy for r/r MM, in H2 2022.
CB-020: Caribou expects to announce target selection for CB-020, an iPSC-derived CAR-NK cell therapy for solid tumors, in Q4 2022. Additionally, Caribou expects to disclose multiple armoring strategies under development for its CAR-NK platform in Q4 2022.
CB-012: Caribou expects to submit an IND application for CB-012, an anti-CD371 CAR-T cell therapy for r/r AML, in 2023.
Upcoming Meetings

May 16-19, 2022: 25th Annual Meeting of the American Society for Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper). A poster with data highlighting the mechanism underlying the superior specificity of its CRISPR hybrid RNA-DNA (chRDNA) guides for genome editing of primary human T cells will be presented on Monday, May 16, 2022, 5:30 – 6:30 pm ET
June 9-17: European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress. Initial ANTLER Phase 1 clinical data for CB-010 is scheduled to be presented
June 23-24: SingHealth Duke-NUS Cell Therapy Centre (SDCT) and Regenerative Medicine Institute of Singapore (REMEDIS) Annual Conference. An encore presentation of initial ANTLER data will be presented
July 18-22: Pan Pacific Lymphoma Conference 2022. An encore presentation of initial ANTLER data will be presented
First Quarter 2022 Financial Results

Cash, cash equivalents, and marketable securities: Caribou had $390.8 million in cash, cash equivalents, and marketable securities as of March 31, 2022 compared to $413.5 million as of December 31, 2021.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $2.7 million for the three months ended March 31, 2022 compared to $1.6 million for the same period in 2021. The increase was primarily due to an increase in revenue recognized pursuant to the AbbVie collaboration and license agreement.

R&D expenses: Research and development expenses were $13.9 million for the three months ended March 31, 2022 compared to $10.2 million for the same period in 2021. The increase was primarily due to personnel-related expenses attributable to increased headcount, costs associated with clinical trial and preclinical study activities, and facilities expenses, partially offset by a decrease in expenses related to licensing, sublicensing revenue, and milestones.

G&A expenses: General and administrative expenses were $9.6 million for the three months ended March 31, 2022 compared to $4.6 million for the same period in 2021. The increase was primarily due to personnel-related expenses attributable to increased headcount, legal and accounting services, insurance, other expenses associated with operating as a public company, and facilities and other expenses.

Other income (expense): The Company recorded other income of $1.8 million for the three months ended March 31, 2022 compared to less than $0.1 million for the same period in 2021. This increase was primarily due to the non-cash change in fair value of the success payments liability under the Memorial Sloan Kettering Cancer Center (MSKCC) exclusive license agreement.

Net loss: For the three months ended March 31, 2022, net loss was $19.1 million compared to $13.2 million for the same period in 2021.

About Caribou’s Novel Next-Generation CRISPR Platform
CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems are capable of editing unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On May 9, 2022 Singapore-based SCG Cell Therapy Pte Ltd ("SCG"), a leading biotechnology company, reported that Singapore’s Health Sciences Authority (HSA) has cleared the company’s Investigational New Drug (IND) application for clinical trials for SCG101 – an autologous T-cell receptor (TCR) T-cell therapy (Press release, SCG Cell Therapy, MAY 9, 2022, View Source [SID1234614172]). SCG101 is being developed to treat hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) – the most common form of liver cancer.

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The treatment has recently secured IND approval from China’s National Medical Products Administration (NMPA), making it the first TCR-T cell therapy product approved by the NMPA for the treatment of HCC and the first multi-regional IND approval in the field of cell therapy across Singapore and China.

"The multi-country IND approval for SCG101 is a key milestone for SCG’s cell therapy pipeline, proving our capability to fulfil regulatory requirements in the target markets", said Frank Wang, Chief Executive Officer of SCG Cell Therapy. "Globally, liver cancer has the second-highest cancer-mortality rate accounting for over 700,000 deaths each year. Four in five new HCC cases are diagnosed in the Asia Pacific. Singapore is known as a medical centre of excellence in Southeast Asia and is one of the world’s top medical tourism destinations. This milestone pushes forward our mission to advance cell therapy to patients in need and strengthens our position as a key global player", Frank added.

"In Singapore, liver cancer is the third most common cause of cancer-related death. There are significant challenges with the available treatment options in meeting patient needs. SCG101 offers a novel treatment option for patients," said Dr Yong Wei Peng, Principal Investigator of the study and Senior Consultant at the Department of Haematology-Oncology at the National University Cancer Institute, Singapore.

"Cell therapy is one of the most promising and rapidly advancing treatments for chronic and life-threatening diseases such as cancer. SCG101, an individualised cancer treatment which is manufactured locally at Cell Therapy Facility of Singapore Health Sciences Authority (HSA-CTF), offers potential new hope to such cancer patients in Singapore," said Dr Toh Han Chong, Principal Investigator at National Cancer Centre Singapore.

According to Grand View Research, the global T-cell therapy market is expected to reach USD 20.3 billion by 2028, expanding at a CAGR of 20.2% from 2021 to 2028.

With SCG101, the function of T-cells is activated by recognising peptide fragments – short chains of amino acids – of pathogen-derived proteins in the form of complexes of peptides and MHC molecules (major histocompatibility complex) on the cell surface via the TCR. SCG101 specifically recognises the epitope of the hepatitis B virus surface antigen (HBsAg), which redirects T-cells specificity against the HBV antigens. With the specific HLA typing, SCG101 can recognise both HBsAg membrane antigen and HBsAg intracellular antigen. Therefore, SCG101 eliminates HBsAg-positive HCC cells and also eradicates HBV cccDNA (covalently closed circular DNA).

T-cells are important white blood cells of the immune system and play a central role in the adaptive immune response. TCRs are molecules on the surface of T-cells that allow the immune system to distinguish the body’s own healthy cells from diseased pathogen-infected or tumour cells.

In November 2021, SCG Cell Therapy announced a collaboration with the Cell Therapy Facility of Singapore’s Health Sciences Authority (HSA-CTF) for the evaluation and validation of SCG’s proprietary cell therapy manufacturing process for the development of new treatment options for patients with HBV related HCC.

The validation process of SCG101 was performed in the Good Manufacturing Practice (GMP)-certified facility at HSA-CTF and is fully compliant with current GMP (cGMP) requirements.