On March 26, 2024 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported fourth quarter and annual financial results and business highlights for the year ended December 31, 2023, including recent commercial and operational progress (Press release, bluebird bio, MAR 26, 2024, View Source [SID1234641439]).

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"In 2023, bluebird established a validated, commercial gene therapy strategy that brought ZYNTEGLO and SKYSONA to individuals living with beta-thalassemia and cerebral adrenoleukodystrophy. Building on that foundation, today we are positioned for robust commercial uptake of LYFGENIA for sickle cell disease, with a substantial QTC network in place, favorable Medicaid coverage being established, and demonstrated strong patient demand," said Andrew Obenshain, chief executive officer, bluebird bio. "Our recent agreement with Hercules Capital meaningfully extends our cash runway, and further enables us to capitalize on our commercial head start and bring our transformative gene therapies to patients and their families. In 2024, we anticipate between 85 to 105 patient starts across our three FDA approved therapies, laying the foundation for strong revenue growth."

RECENT COMPANY HIGHLIGHTS

Up to $175 million Debt Financing with Hercules Capital

On March 18, 2024, bluebird announced that it had entered into a five-year term loan facility with Hercules Capital. Under the terms of the agreement, the Company may draw up to $175 million, available in four tranches. The first tranche of $75 million was drawn at closing. The Company may draw upon two additional tranches of $25 million each, subject to satisfaction of certain conditions, including achievement of commercial milestones. The facility also provides for a fourth tranche of $50 million, available at the lender’s discretion.
Based on launch estimates and current business plans, and assuming three tranches totaling $125 million are executed, the transaction is projected to extend the Company’s cash runway through Q1 2026.
COMMERCIAL LAUNCH UPDATES

Strong patient uptake across portfolio

First LYFGENIA patient start imminent; multiple patients enrolled and preparing for treatment across QTC network.
Continued strong, linear growth for ZYNTEGLO with 7 patient starts since the beginning of 2024, in addition to 20 patient starts completed for ZYNTEGLO in 2023.
Completed 2 patient starts for SKYSONA since the beginning of 2024, in addition to 6 patient starts completed for SKYSONA in 2023.
Validated access and reimbursement strategy is driving favorable coverage landscape

In the first quarter of 2024, bluebird signed its first Medicaid outcomes-based agreement for LYFGENIA with the state of Michigan.
In addition to the Medicaid outcomes-based agreement, bluebird has signed four outcomes-based agreements for LYFGENIA with national commercial payer organizations and published coverage policies cover more than 200 million U.S. lives.
Discussions are ongoing with more than 15 Medicaid agencies representing 80% of Medicaid-insured individuals with sickle cell disease in the U.S. and the Company is engaged with the Center for Medicare and Medicaid Innovation (CMMI) on its Cell and Gene Therapy Access Model demonstration.
Timely access to ZYNTEGLO and SKYSONA has continued, with zero ultimate denials for either therapy across both Medicaid and commercial payers.
Substantial QTC footprint established

bluebird has activated 62 QTCs for ZYNTEGLO (defined as a signed MSA); capitalizing on launch synergies, 49 centers are already receiving referrals for LYFGENIA.
Five centers are also activated to administer SKYSONA for patients with cerebral adrenoleukodystrophy (CALD).
The Company anticipates continued QTC network expansion across its portfolio in 2024.
LOVO-CEL CLINICAL TRIAL UPDATE

Enrollment is ongoing for the HGB-210 study evaluating lovo-cel for patients under the age of 12. The Company anticipates enrollment to be complete in Q4 2024.
2024 GUIDANCE

The Company anticipates 85 to 105 patient starts (cell collections) combined across all three of its FDA approved therapies (LYFGENIA, ZYNTEGLO, SKYSONA) in 2024. Consistent with previous quarters, bluebird plans to provide quarterly updates on patient starts for each of its therapies.
Gross-to-net discounts across all three products are expected to be in the range of 20% to 25% of gross revenue in 2024 and will fluctuate based on product and payer mix, and well as utilization of outcomes-based agreements for LYFGENIA and ZYNTEGLO.
Based on projected timelines from cell collection to infusion, the Company expects to recognize revenue from its first infusion of LYFGENIA in the third quarter of 2024.
FOURTH QUARTER AND ANNUAL FINANCIAL HIGHLIGHTS

Cash Position: The Company’s cash, cash equivalents and restricted cash balance was approximately $275 million, including restricted cash of approximately $53 million, as of December 31, 2023.

Based on launch trajectory and current business plans, bluebird expects its cash and cash equivalents excluding restricted cash and assuming three tranches totaling $125 million in proceeds from its term loan facility are executed, will be sufficient to meet bluebird’s planned operating expenses and capital expenditure requirements through Q1 2026.

In the fourth quarter of 2023, the Company entered into a factoring agreement which is accelerating cash collection related to patient starts across its portfolio of approved therapies.
Revenue, net: Total revenue, net was $7.8 million for the three months ended December 31, 2023, compared to $0.1 million for the three months ended December 31, 2022.

Total revenue, net was $29.5 million for the twelve months ended December 31, 2023, compared to $3.6 million for the twelve months ended December 31, 2022. The increase of $25.9 million was primarily due to SKYSONA and ZYNTEGLO product revenue.

For the year ended December 31, 2023, product revenues by therapy represent $16.7 million attributable to ZYNTEGLO and $12.4 million attributable to SKYSONA, with gross-to-net discounts of approximately 19% across both products.
On March 26, 2024, bluebird announced that it will restate its consolidated financial statements for 2022, and for the first three quarters of both 2022 and 2023 in its Annual Report on Form 10-K for the year ended December 31, 2023 (the "2023 Form 10-K"). The restatements relate to the identification of embedded leases and the treatment of non-lease components contained in lease agreements with contract manufacturers. As a result, the Company anticipates recording an increase in lease assets and lease liabilities, as well as an increase in non-cash interest expense in each restated period. The Company does not expect the restatement to result in any impact on its cash position or revenue. bluebird anticipates filing its 2023 Form 10-K, inclusive of the restatement no later than April 16, 2024.

The financial results included in this press release represent the most current information available to the Company’s management. The Company expects that its actual results to be reported in its 2023 Form 10-K will not differ materially from the results included herein, however, these results are subject to change following the completion of the Company’s financial close procedures and the audit of its consolidated financial statements for the year ended December 31, 2023.

CONFERENCE CALL DETAILS

bluebird will hold a conference call to discuss its fourth quarter and 2023 annual results and business updates today, Tuesday, March 26, 2024, at 8:00 am ET.

To access the live conference call via telephone, please register at this link to receive a dial in number and unique PIN.

The live webcast of the call may be accessed by visiting the "Events & Presentations" page within the Investors & Media section of the bluebird website at View Source A replay of the webcast will be available on the bluebird website for 90 days following the event.

On March 26, 2024 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a commercial stage biopharmaceutical company pursuing life-changing therapies in oncology and rare diseases, reported its financial results for the year ended December 31, 2023, and provided recent corporate and portfolio updates (Press release, BioLineRx, MAR 26, 2024, https://ir.biolinerx.com/news-releases/news-release-details/biolinerx-reports-2023-financial-results-and-recent-corporate [SID1234641438]).

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"Following FDA approval of APHEXDA in September, physicians and transplant centers have been very receptive to the value of our strong clinical data, and our commercial team has made substantial progress establishing relationships with transplant centers across the country," said Philip Serlin, Chief Executive Officer of BioLineRx. "This year will continue to be primarily a foundational period for the commercialization of APHEXDA. We are seeing substantial progress on Pharmacy & Therapeutics committee approvals — the first step toward center adoption — and are actively supporting centers as they build usage protocols and treat their first patients. Initial feedback on patient experiences has been positive, and we are already seeing repeat purchases. Notably, we have achieved payer coverage representing approximately 95% of covered lives in the U.S. to date, which we believe reflects the value that APHEXDA offers to payers and patients alike, particularly its ability to mobilize the targeted number of stem cells in fewer apheresis sessions.

"Additionally, through a clinical collaboration with Washington University, we are actively evaluating the potential of motixafortide to support gene therapy for patients with sickle cell disease, a treatment process that requires significant quantities of hematopoietic stem cells. We anticipate data from this proof-of-concept Phase 1 study in patients with sickle cell disease in the second half of this year.

"At the same time, we are making significant progress advancing clinical programs evaluating motixafortide in pancreatic cancer, which if ultimately approved in combination with PD-1 inhibitors, would serve a much larger patient population and provide confidence for expanding into additional solid tumors. In pancreatic cancer, our enthusiasm is bolstered by the compelling data presented last fall from the single-arm pilot phase of the Phase 2b trial sponsored by Columbia University. The first patient has now been dosed in the randomized Phase 2b portion of that study, and we are also working with Gloria Biosciences on the design and execution of a similar randomized Phase 2b combination trial of motixafortide and zimberelimab in pancreatic cancer in China.

"Our vision of bringing a best-in-class stem cell mobilization agent to market, as well as advancing development in pancreatic cancer and other solid tumor areas with major unmet needs, is being actively realized. We look forward to the exciting, continued execution progress that our commercial and development teams will make this year," Mr. Serlin concluded.

Corporate Updates

Launched APHEXDA (motixafortide) in the U.S.
Announced closing of exclusive license agreement that includes development and commercialization rights to motixafortide across all indications in the Asia region, as well as a strategic equity investment
Strengthened motixafortide intellectual property estate with notice of allowance for U.S. patent covering method of manufacturing motixafortide suitable for large scale production; the patent supplements existing Orphan Drug Designation in the U.S. and Europe for the treatment of pancreatic cancer, as well as Orphan Drug market exclusivity for autologous stem cell mobilization in multiple myeloma patients in the U.S. following last year’s FDA approval of APHEXDA
APHEXDA Launch Updates

Reported positive coverage decisions by payers representing ~95% of all covered lives in the U.S.
Received inclusion of APHEXDA in the National Comprehensive Cancer Network (NCCN) guidelines for Hematopoietic Cell Transplantation
Achieved "on formulary" status for APHEXDA within targeted top 80 transplantation centers (which perform 85% of all U.S. transplants) managing ~20% of stem cell transplant procedures at these institutions; anticipate similar on formulary status of ~35% at end of Q2 2024 and ~60% at year-end 2024
Received Healthcare Common Procedure Coding System (HCPCS) J-Code to facilitate Medicare reimbursement for APHEXDA to transplant centers treating Medicare beneficiaries
Clinical Portfolio Updates

Motixafortide (selective inhibitor of CXCR4 chemokine receptor)

Multiple Myeloma

Presented posters at both the American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Meeting on December 10, 2023, and the 2024 Tandem Meetings on February 21-24, 2024. The posters reviewed combination premedication benefits in the Phase 3 GENESIS trial, extended PD effect of elevated CD34+ cells in peripheral blood, and a post-hoc subgroup analysis of impaired HSC mobilization patients that demonstrated a consistent benefit of motixafortide + G-CSF over placebo + G-CSF mobilization for all patients
Supported collaboration partner Gloria Biosciences with stem cell mobilization bridging study IND filing in February with the Center for Drug Evaluation of the National Medical Products Administration in China. Anticipate regulatory action in May 2024 and initiation of pivotal clinical trial in 2H 2024
Pancreatic Ductal Adenocarcinoma (mPDAC)

Announced first patient dosed in a randomized, investigator-initiated Phase 2b clinical trial in collaboration with Columbia University assessing motixafortide in combination with the PD-1 inhibitor cemiplimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer
Advanced plans with collaboration partner Gloria Biosciences on a Phase 2b randomized clinical trial in China assessing motixafortide in combination with the PD-1 inhibitor zimberelimab and standard-of-care chemotherapy as first-line treatment in patients with metastatic pancreatic cancer. Anticipate clinical trial initiation in 2025
Sickle Cell Disease (SCD) & Gene Therapy

Continued to enroll patients into a clinical trial in collaboration with Washington University School of Medicine in St. Louis to evaluate motixafortide as monotherapy and in combination with natalizumab for stem cell mobilization for gene therapies in sickle cell disease. Anticipate data in 2H 2024
Financial Results for Year Ended December 31, 2023

Total revenues for the year ended December 31, 2023, were $4.8 million, compared to no revenues for the year ended December 31, 2022. Revenues in 2023 (all of which were recorded in the fourth quarter) primarily reflect a portion of the upfront payment from the Gloria Biosciences license agreement, of which $4.6 million was recognized in 2023, as well as $0.2 million of revenues from product sales of APHEXDA in the U.S.
Cost of revenues for the year ended December 31, 2023, amounted to $3.7 million, compared to no cost of revenues for the year ended December 31, 2022. The cost of revenues in 2023 (all of which was recorded in the fourth quarter) primarily reflects a $3.0 million sub-license fee to the upstream licensor of motixafortide payable on closing of the exclusive license agreement in Asia, as well as amortization of an intangible asset in respect of these license revenues in the amount of $0.5 million. Cost of product sales were insignificant, representing approximately 6% of related sales.
Research and development expenses for the year ended December 31, 2023, were $12.5 million, compared to $17.6 million for the year ended December 31, 2022. The decrease resulted primarily from lower expenses related to motixafortide NDA supporting activities, as well as lower expenses associated with completion of the AGI-134 study
Sales and marketing expenses for the year ended December 31, 2023, were $25.3 million, compared to $6.5 million for the year ended December 31, 2022. The increase resulted primarily from the ramp-up of pre-commercialization and commercialization activities related to motixafortide
General and administrative expenses for the year ended December 31, 2023, were $6.3 million, compared to $5.1 million for the year ended December 31, 2022. The increase resulted primarily from an increase in payroll and related expenses associated with a small headcount increase during the 2022 period, as well as an increase in professional services and legal expenses
Non-operating expenses for the year ended December 31, 2023, were $10.8 million, compared to non-operating income of $5.7 million for the year ended December 31, 2022. Non-operating expenses and income primarily relate to the non-cash revaluation of outstanding warrants resulting from changes in the company’s share price during the respective periods
Net loss for the year ended December 31, 2023 was $60.6 million, compared to $25.0 million for the year ended December 31, 2022. The net loss for 2023 included $17.8 million in non-cash expenses, specifically an expense of $11.1 million for the revaluation of warrants and a one-time $6.7 million impairment of intangible assets associated with discontinuation of the AGI-134 development program. The net loss for 2022 included $6.4 million in non-cash income specifically related to the revaluation of warrants.
As of December 31, 2023, the Company had cash, cash equivalents, and short-term bank deposits of $43.0 million. The Company anticipates that this amount and other available resources, including amounts available under a debt facility with Kreos Capital, will be sufficient to fund operations, as currently planned, into 2025
A copy of the Company’s annual report on Form 20-F for the year ended December 31, 2023 has been filed with the U.S. Securities and Exchange Commission at View Source and posted on the Company’s investor relations website at View Source Company will deliver a hard copy of its annual report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request at [email protected].

Conference Call and Webcast Information

To access the conference call, please dial +1-888-281-1167 from the U.S. or +972-3-918-0685 internationally. A live webcast and a replay of the call can be accessed through the event page on the Company’s website. Please allow extra time prior to the call to visit the site and download any necessary software to listen to the live broadcast. The call replay will be available approximately two hours after completion of the live conference call. A dial-in replay of the call will be available until March 28, 2024; please dial +1-888-295-2634 from the US or +972-3-925-5904 internationally.

On March 26, 2024 Ayala Pharmaceuticals, Inc. (OTCQX: ADXS), a clinical-stage oncology company, reported the completion of the previously announced sale of AL102, and related drug candidate AL101, to Immunome, Inc. (Nasdaq: IMNM) (Press release, Ayala Pharmaceuticals, MAR 26, 2024, View Source [SID1234641437]).

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As per the terms of the sale, Ayala received from Immunome $20 million in cash and 2,175,489 shares of Immunome common stock, and Immunome assumed specified liabilities related to AL102. Ayala may also receive up to an additional $37.5 million in development and commercial milestone payments.

"We are pleased that AL102 will now be advanced by the highly experienced team at Immunome," said Ken Berlin, President and CEO of Ayala Pharmaceuticals. "I am deeply grateful to the team at Ayala for the work they have done over the last several years to assemble compelling clinical data and reach this point."

A.G.P./Alliance Global Partners acted as strategic advisor to Ayala Pharmaceuticals, Inc. in connection with the transaction.

On March 26, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported financial results for the three months and year ended December 31, 2023, and provided a corporate update (Press release, Aptose Biosciences, MAR 26, 2024, View Source [SID1234641436]).

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"The data we have generated from tuspetinib thus far – as a single agent and in combination therapy with venetoclax in relapsed and refractory AML – have demonstrated a distinctly favorable safety profile and broad activity for tuspetinib across mutational subtypes. This profile also extends to FLT3 wildtype AML, which represents the majority of AML patients, and in which few agents have shown such broad activity," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "These data have propelled us to initiate a clinical study of tuspetinib in a triplet combination with venetoclax and azacitidine in frontline therapy for newly diagnosed AML, including both FLT3 wild type and FLT3 mutated subtypes."

Key Corporate Highlights

Aptose Completes Public Offering – On January 30, 2024, Aptose closed a public offering of 5,649,122 common shares of the Company and warrants at a combined offering price of US $1.71 per share. This included 736,842 Common Shares and warrants pursuant to a full exercise by the underwriter of its over-allotment option. Total gross proceeds from the public offering were approximately $9.7 million before deducting underwriting costs, placement agent commissions and other offering-related expenses.

Private Placement – On January 31, 2024, Aptose closed a US $4 million private placement of common shares with strategic partner Hanmi Pharmaceutical. Under the terms of the strategic investment, Hanmi purchased each common share at a price of US $1.90, representing an 11% premium over the price of the common shares issued as part of the public offering. The Company also issued Hanmi warrants to purchase common shares at an exercise price of US $1.71 per warrant share. Total gross proceeds from the private placement were approximately $4 million, excluding underwriting discounts, placement agent commissions and other offering-related expenses.

Tuspetinib Advancing to Triplet Therapy Pilot Study – Tuspetinib (TUS), a once daily oral agent with a unique kinase targeting pattern, is being developed for the treatment of patients with acute myeloid leukemia (AML). More than 170 patients to date received TUS alone or in combination with the BCL-2 inhibitor venetoclax (VEN) during the Phase 1/2 clinical program in the very ill relapsed or refractory (R/R) AML patient population. At the single agent 80 mg recommended Phase 2 dose, TUS achieved a favorable safety profile and a CR/CRh rate of 36% among patients who were naive to VEN. The safety profile of TUS remained favorable when TUS was combined with VEN in R/R AML patients, and responses were achieved in both patients naive to VEN and those who failed prior therapy with VEN. TUS avoids many typical toxicities observed with other agents and achieves broad activity across AML patients with a diversity of adverse genetics. Tuspetinib is now being advanced to a triplet combination therapy of tuspetinib, venetoclax and a hypomethylating agent (TUS/VEN/HMA) for the frontline treatment of newly diagnosed AML patients ineligible for induction chemotherapy.

Luxeptinib G3 Evaluation Completed – During 2023 and early 2024, clinical evaluation of the new generation 3 (G3) formulation of luxeptinib (LUX) was completed. The G3 formulation was tested in a single dose bioavailability study in 20 patients, including both B-cell cancer and AML patients, and across 5 dose levels (10mg to 200mg). The G3 formulation then was evaluated in R/R AML patients with continuous dosing using two different dose levels (50mg BID and 200mg BID) in a total of 11 patients. Data show the G3 formulation dosed at 200mg twice daily can achieve 2-3uM steady state plasma levels, with approximately 10-fold better absorption, and interestingly even better tolerability, than the original G1 formulation. Thus, the G3 formulation achieved the desired plasma exposure benchmark and can serve as the formulation of choice for future studies with LUX. Aptose is exploring alternative development paths and collaborations to advance LUX as a single agent or in combination with VEN to treat defined R/R patient populations of high unmet need.
Multiple Planned Value-creating Milestones Ahead

TUS/VEN doublet synopsis in R/R AML: EHA (Free EHA Whitepaper) 2024
TUS/VEN/HMA planned initiation of pilot triplet study in 1L AML: Summer 2024
Triplet pilot dose escalation planned with early CR/MRD/safety data in 1L AML: ASH (Free ASH Whitepaper) 2024
Triplet pilot completed with CR/MRD data and dose selection: EHA (Free EHA Whitepaper) 2025
Triplet initiation of Ph2/Ph3 pivotal program: 2H 2025
FINANCIAL RESULTS OF OPERATIONS

Balance Sheet Data
(unaudited)
($ in thousands)

December 31, December 31,
2023 2022
Cash, cash equivalents and short-term investments $ 9,252 $ 46,959
Working capital (3,375 ) 37,235
Total assets 12,989 51,027
Non-current liabilities 621 1,002
Deficit (515,537 ) (464,330 )
Total shareholders’ equity (2,901 ) 37,741

Cash and cash equivalents, January 31, 2024 (unaudited) was $18.6 million, after gross proceeds from January 2024 financings (unaudited) of $13.7 million.
Total cash and cash equivalents and investments as of December 31, 2023, were $9.3 million, a decrease of $37.7 million as compared to $47.0 million at December 31, 2022. Based on current operations, the Company expects that cash on hand and available capital provide the Company with sufficient resources to fund planned Company operations including research and development through August of 2024.
Working capital is a non-GAAP measure and represents cash, cash equivalents, investments, prepaid expenses and other current assets less current liabilities.
Common shares issued and outstanding as at March 26, 2024 were 15,717,701.

Statements of Operations Data
(unaudited)

Year ended December 31,
(in thousands except per Common Share data) 2023
2022

Revenues $ - $ -
R&D, related party 3,492 3,556
Research and development expenses 33,273 24,532
General and administrative expenses 15,591 14,514
Net finance income 1,149 779
Net loss $ (51,207 ) $ (41,823 )
Basic and diluted loss per Common Share $ (7.58 ) $ (6.80 )
Weighted average number of common shares outstanding used in the calculation of basic loss per share 6,755 6,151

Net loss for the year ended December 31, 2023 increased by $9.4 million to $51.2 million, as compared to $41.8 million for the comparable period in 2022.

Research and Development Expenses

The research and development expenses for years ended December 31, 2023, and 2022 are as follows:

Twelve months ended
December 31,
(in thousands) 2023 2022

Program costs – Tuspetinib $ 24,925 $ 10,083
Program costs – Luxeptinib 3,510 8,426
Program costs – APTO-253 40 141
Personnel related expenses 6,878 7,181
Stock-based compensation 1,373 2,218
Depreciation of equipment 39 39
Total $ 36,765 $ 28,088

R&D expenses increased by $8.7 million to $36.8 million for the year ended December 31, 2023, as compared with $28.1 million for the comparative period in 2022. Changes to the components of our R&D expenses presented in the table above are primarily related to the following activities:

Program costs for tuspetinib increased by $14.8 million. The higher program costs for tuspetinib in 2023 represent the enrollment of patients in our APTIVATE clinical trial, our healthy volunteer trial, manufacturing activities to support clinical development, purchase of clinical trial materials, and related expenses.
Program costs for luxeptinib decreased by approximately $4.9 million, primarily due to lower clinical trial costs and lower manufacturing costs as a result of the current formulation requiring less API than the prior formulation.
Program costs for APTO-253 decreased by approximately $101 thousand due to the Company’s decision on December 20, 2021, to discontinue further development of APTO-253.
Personnel-related expenses decreased by $0.3 million due to lower headcount in 2023.
Stock-based compensation decreased by approximately $845 thousand in the year ended December 31, 2023, compared with the year ended December 31, 2022, primarily due to stock options granted with lower grant date fair values in the current period.
General and Administrative Expenses

General and administrative expenses consist primarily of salaries, benefits, and travel, including stock-based compensation for our executive, finance, business development, human resources, and support functions. Other general and administrative expenses and professional fees include 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 associated with being a publicly traded company and to support 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 years ended December 31, 2023 and 2022 are as follows:

Year ended December 31,
(in thousands) 2023 2022
General and administrative, excluding items below: $ 13,262 $ 11,444
Stock-based compensation 2,280 2,989
Depreciation of equipment 49 81
Total $ 15,591 $ 14,514

General and administrative expenses increased by approximately $1.1 million $15.6 million for the year ended December 31, 2023, as compared with $14.5 million for the comparative period in 2022. The increase was primarily as a result of higher salaries expenses, higher professional fees, and higher travel expenses, partly offset by a decrease in stock-based compensation costs.

Stock-based compensation decreased by $709 thousand mostly as a result of options having a lower grant date fair value as compared with the options granted in the comparative period.

Conference Call & Webcast:
Date: Tuesday, March 26, 2024
Time: 5:00 PM ET
Audio Webcast Only: link
Q&A Participant Registration Link*: link
(https://register.vevent.com/register/BIe69f08fc83634a6aa38bf7081d82c6a2)

*Analysts interested in participating in the question-and-answer session will pre-register for the event from the participant registration link above to receive the dial-in numbers and a unique PIN, which are required to access the conference call. They also will have the option to take advantage of a Call Me button and the system will automatically dial out to connect to the Q&A session.

The audio webcast also can be accessed through a link on the Investor Relations section of Aptose’s website here. A replay 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 year ended December 31, 2023 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

On March 26, 2024 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a business update (Press release, Aprea, MAR 26, 2024, View Source [SID1234641435]).

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"Aprea had a very productive 2023 with significant progress across our diversified pipeline of synthetic lethality-based cancer therapeutics. We are pleased to continue this positive momentum in 2024 and focus on the execution on our programs towards successfully delivering potentially safer and more effective therapies for cancer patients," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "We continue to enroll and treat patients in the ongoing Phase 1/2a study of our novel macrocyclic ATR inhibitor, ATRN-119. ATRN-119 appears to be well tolerated with a manageable toxicity profile. Dose escalation will proceed throughout 2024 with potential for human efficacy data in the second half of the year. We are preparing to enter the clinic with our next generation inhibitor of WEE1 kinase, APR-1051, having received clearance from the FDA on our IND. Based on the unique characteristics of APR-1051 we believe it will be best in class."

Dr. Gilad continued "the closing of our recent private placement financing provides us with the capital to fund both of these lead programs through meaningful clinical milestones. I would like to thank our dedicated team, our academic collaborators, as well as existing and new investors who have supported our recent advancements. Our mission is to be a global leader in synthetic lethality and we see a great opportunity to help cancer patients in need and create value for our shareholders."

Key Business Updates and Potential Upcoming Key Milestones

ATR inhibitor, ATRN-119, on track to complete monotherapy dose escalation end of the year; initial efficacy data expected in second half of 2024

ATRN-119 is a potent and highly selective first-in-class macrocyclic ATR inhibitor, designed to be used in patients with mutations in DDR-related genes. Cancers with mutation in DDR-related genes represent a high unmet medical need. Patients with DDR-related gene mutations have poor prognosis and, currently, have no effective therapies.
In January 2023, enrollment commenced in an open-label Phase 1/2a clinical trial of ATRN-119 (study AR-276-010) as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. In the ongoing monotherapy dose escalation phase (Part 1) of the trial, the primary endpoint is evaluating the tolerability and pharmacokinetics of continuous daily oral dosing of ATRN-119 using a 3+3 trial design in up to approximately 30 patients. A secondary endpoint is evaluating potential initial efficacy.
An update from Part 1 of the trial was featured in a poster presentation at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference in October 2023.
As of January 2, 2024, 12 patients were enrolled to the first four cohorts of the Phase 1 escalation stage (50mg/day, 100mg/daily, 200mg/daily and 350mg/daily). ATRN-119 was found to be safe and well tolerated in all four cohorts, with no related adverse effects > grade 2. The most recent efficacy analysis conducted at that date shows that two patients achieved stable disease – one each in the 50 mg and 200 mg cohorts. Both these patients’ tumors have mutations that have been predicted to confer sensitivity to ATR inhibition.
As of March 26, 2024 four clinical sites have been activated in the US. At completion of Part 1 of the study, the company anticipates identification of a recommended Phase 2 dose (RP2D) that will be used in a Phase 2a cohort expansion (Part 2) to test the tolerability and potential efficacy of ATRN-119 monotherapy in approximately 30 additional patients. The Phase 1 dose escalation is expected to be completed in 4Q 2024, and RP2D is to be determined in 1Q 2025. Enrollment in the Phase 2a cohort is expected to begin in 1Q 2025 with additional efficacy data expected in 3Q 2025.
A more comprehensive dataset from Part 1 of the study has been accepted for presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2024.
For more information, please refer to clinicaltrials.gov NCT04905914.

Oral WEE1 inhibitor, APR-1051, expected to enter Phase 1 clinical trial in the first half of 2024

APR-1051 is a potent and selective small molecule that has the potential to avoid off target toxicity and achieve greater clinical activity than other WEE1 programs currently in development. Aprea is advancing APR-1051 as monotherapy in ovarian cancer with Cyclin E over expression. Cancers over expressing Cyclin E represent a high unmet medical need. Patients with Cyclin E over expression have poor prognosis and, currently, have no effective therapies.
In March 2024, the U.S. FDA cleared the Investigational New Drug (IND) application (IND 169359) for APR-1051. Clearance of this IND will allow Aprea to initiate the Phase 1 ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) trial. This dose escalation trial will evaluate the safety, tolerability, and preliminary efficacy of APR-1051. Enrollment of the first patient is expected in H1 2024 with an update expected in the Q4 2024.
Preclinical data on APR-1051 were presented in a poster at the AACR (Free AACR Whitepaper)-NCI-EORTC International Conference in October 2023. The data highlighted the selectivity of APR-1051 with low off-target activity against PLK1, PLK2 and PLK3, a family of kinases that promote M phase entry, a critical phase in the cell cycle. APR-1051 showed potentially favorable PK properties and appears to cause lower inhibition of hERG, a potential indication of low cardiotoxicity. At doses and scheduling that suppress tumor growth, APR-1051 causes little anemia. The selectivity of APR-1051 may solve a long-standing problem with other WEE1 inhibitors. Recent studies indicate that PLK1 off-targeting partially counters the intracellular effects of WEE1 inhibition and could potentially contribute to the myelosuppression observed with other WEE1 inhibitors.

Pipeline – lead candidate for a third synthetic lethality program to be selected in 2024

Aprea’s research and development team has identified a new target in synthetic lethality. Our discovery team is developing a series of molecules that are selective and potent against it.
A lead molecule is expected to be declared in 2Q 2024.
This program may provide clinically meaningful differences for cancer patients that currently have limited therapies.

KOL Event

Hosted a Key Opinion Leader (KOL) event on October 31, 2023, highlighting the Company’s portfolio of small molecules focused on Synthetic Lethality (SL) by targeting the DNA Damage Response (DDR) Pathways. The event featured Key Opinion Leaders Dr. Fiona Simpkins, Professor in the Division of Gynecology Oncology and Department of OB-GYN at the University of Pennsylvania, Dr. Timothy Yap, medical oncology physician-scientist and Professor at the University of Texas MD Anderson Cancer Center, Dr. Eric Brown, a consultant to Aprea and a Professor at the University of Pennsylvania and a member of the Abramson Family Cancer Research Institute, and Aprea’s Dr. Nadeem Mirza, Senior Medical Advisor. The speakers, along with the management team, provided an overview of the Company’s lead ATR inhibitor candidate, ATRN-119, and its WEE1 inhibitor candidate, APR-1051, and highlighted the addressable unmet clinical need and potential combination therapies using these programs. A replay of the event can be access on the Aprea corporate website here.

Select Financial Results for the Fourth Quarter ended December 31, 2023

As of December 31, 2023, Aprea reported cash and cash equivalents of $21.6 million.
For the quarter ended December 31, 2023, the Company reported an operating loss of $3.7 million, compared to an operating loss of $2.7 million in the fourth quarter of 2022.
Research and Development (R&D) expenses were $2.0 million for the quarter ended December 31, 2023, compared to $0.5 million for the fourth quarter of 2022. The increase in R&D expense was primarily related to the Phase 1/2a clinical trial evaluating ATRN-119 which enrolled its first subject in Q1 2023 and IND enabling studies for APR-1051, the Company’s small molecule WEE1 inhibitor.
General and Administrative (G&A) expenses were $1.6 million for the quarter ended December 31, 2023, compared to $2.1 million for the comparable period in 2022. The decrease in G&A expenses was primarily due to a decrease in personnel costs and insurance premiums.
The Company reported a net loss of $3.4 million ($0.92 per basic share) on approximately 3.7 million weighted-average common shares outstanding for the quarter ended December 31, 2023, compared to a net loss of $2.4 million ($0.92 per basic share) on approximately 2.6 million weighted average common shares outstanding for the comparable period in 2022.

Select Financial Results for the Year ended December 31, 2023

As of December 31, 2023, the Company reported cash and cash equivalents of $21.6 million compared to $28.8 million as of December 31, 2022. The Company believes its cash and cash equivalents as of December 31, 2023, combined with the upfront gross proceeds of approximately $16.0 million received from the Company’s private placement of common stock and warrants in March 2024, before deducting placement agent fees and offering costs of approximately $1.4 million, will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into the third quarter of 2025.
For the year ended December 31, 2023, the Company reported an operating loss of $15.5 million, compared to an operating loss of $113.4 million, which include $76.0 million for acquired in-process research and development, for the year ended December 31, 2022.
Research and Development (R&D) expenses were $7.6 million for the year ended December 31, 2023, compared to $16.4 million for the year ended December 31, 2022. The decrease in R&D expense was primarily related to the close out of our clinical trials of eprenetapopt and APR-246, non-cash stock-based compensation from the acceleration of vesting of all outstanding stock options and restricted stock units in connection with the acquisition of Atrin Pharmaceuticals Inc. in 2022 and personnel costs primarily related to the close out of our research facility in Sweden during 2022.
General and Administrative (G&A) expenses were $8.4 million for the year ended December 31, 2023, compared to $21.0 million for the year ended December 31, 2022. The decrease in G&A expenses was primarily due to a decrease in non-cash stock-based compensation from the acceleration of vesting of all outstanding stock options and restricted stock units in connection with the acquisition of Atrin Pharmaceuticals Inc. in 2022 and insurance premiums.
The Company reported a net loss of $14.3 million ($3.95 per basic share) on approximately 3.6 million weighted-average common shares outstanding for the year ended December 31, 2023, compared to a net loss of $112.7 million ($67.99 per basic share) on approximately 1.7 million weighted average common shares outstanding for the comparable period in 2022.