On August 12, 2024 Abeona Therapeutics Inc. (Nasdaq: ABEO) reported financial results for the second quarter of 2024 and recent corporate progress (Press release, Abeona Therapeutics, AUG 12, 2024, View Source [SID1234645719]).

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"Having completed data generation for nearly all of the Chemistry Manufacturing and Controls deliverables outlined in the Complete Response Letter that we received in April 2024, we are on track to resubmit our Biologics License Application for pz-cel this year and, if approved, bring a treatment option to patients with recessive dystrophic epidermolysis bullosa," said Vish Seshadri, Chief Executive Officer of Abeona.

Second Quarter and Recent Progress

Pz-cel for RDEB

● On August 8, 2024, Abeona completed a Type A meeting with the U.S. Food and Drug Administration (FDA) to discuss Abeona’s forthcoming resubmission of its Biologics License Application (BLA) for prademagene zamikeracel (pz-cel), its investigational first-in-class, autologous cell-based gene therapy currently in development for recessive dystrophic epidermolysis bullosa (RDEB). In pre-meeting communications and during the Type A meeting, Abeona shared data and reports addressing nearly all of the deficiencies noted in the Complete Response Letter (CRL) and gained the FDA’s preliminary alignment pending formal review. For two remaining outstanding items related to sterility assays and identity assays, validation is currently ongoing under protocols that incorporate FDA feedback. Abeona continues to expect to resubmit the BLA in the second half of 2024. Upon acceptance of the BLA, Abeona expects the FDA to set a Prescription Drug User Fee Act (PDUFA) action date six months from the date of submission.

● In April 2024, Abeona received a CRL from the FDA based on the need for additional Chemistry Manufacturing and Controls (CMC) information. In the CRL, the FDA noted that certain additional information needed to satisfy CMC requirements must be resolved before the application can be approved. The CRL did not identify any deficiencies related to the clinical efficacy or clinical safety data in the BLA, and the FDA did not request any new clinical trials or clinical data to support the approval of pz-cel.

● In May 2024, new pz-cel long-term safety data with up to 11 years of follow-up were presented during a late-breaker session at the Society for Investigative Dermatology (SID) Annual Meeting. In July 2024, data on wound healing at various anatomical sites after pz-cel treatment were presented at the Society for Pediatric Dermatology (SPD) Annual Meeting.

U.S. commercial launch preparations for pz-cel

● Abeona continues to make progress on key commercial activities in preparation for a potential U.S. launch for pz-cel, including onboarding discussions with epidermolysis bullosa treatment sites, conducting medical and payer engagement, and building supply chain and enterprise capabilities to support the Company’s transition to a commercial stage company.

Pipeline programs

● In July 2024, Abeona announced a non-exclusive agreement with Beacon Therapeutics, under which Beacon Therapeutics will evaluate Abeona’s patented AAV204 capsid for its potential use in AAV gene therapies for select ophthalmology indications.

Corporate highlights

● In May 2024, Abeona closed a $75 million underwritten securities offering with participation from both new and existing investors.

Second Quarter Financial Results and Cash Runway Guidance

Cash, cash equivalents, short-term investments and restricted cash totaled $123.0 million as of June 30, 2024. As of March 31, 2024, cash, cash equivalents, short-term investments and restricted cash totaled $62.7 million. Net cash used in operating activities was $12.7 million for the three months ended June 30, 2024.

Abeona estimates that its current cash and cash equivalents, short-term investments and restricted cash, as well as its $50 million credit facility, are sufficient resources to fund operations into 2026, before accounting for any potential revenue from commercial sales of pz-cel, if approved, or proceeds from the sale of a Priority Review Voucher (PRV), if awarded by the FDA.

Research and development expenses for the three months ended June 30, 2024 were $9.2 million, compared to $8.5 million for the same period of 2023. General and administrative expenses were $8.6 million for the three months ended June 30, 2024, compared to $5.0 million for the same period of 2023. The increase in general and administrative expenses is primarily due to commercial and launch preparation costs. Net income for the second quarter of 2024 was $7.4 million, including a $24.9 million gain resulting from the quarterly remeasurement of the fair value of warrant liabilities. In the second quarter of 2023, net loss was $16.7 million, including an $8.6 million loss resulting from the quarterly remeasurement of the fair value of warrant liabilities.

Conference Call Details

The Company will host a conference call and webcast on Monday, August 12, 2024, at 8:30 a.m. ET, to discuss the quarter results. To access the call, dial 888-506-0062 (U.S. toll-free) or 973-528-0011 (international) and Entry Code: 678762 five minutes prior to the start of the call. A live, listen-only webcast and archived replay of the call can be accessed on the Investors & Media section of Abeona’s website at View Source The archived webcast replay will be available for 30 days following the call.

On August 12, 2024 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported its financial results for the second quarter ended June 30, 2024 and provided an update on its clinical development pipeline and other corporate developments (Press release, Prelude Therapeutics, AUG 12, 2024, View Source [SID1234645736]).

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"Our team continues to make solid progress towards the Company’s ambitious R&D objectives that we established for 2024 and beyond. We are focused on advancing our two lead clinical programs, including the first-in-class, highly selective SMARCA2 degrader, PRT3789 and a potent and selective CDK9 inhibitor, PRT2527, both on track to report initial clinical results this year," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude.

Dr. Vaddi continued, "We believe that targeting the SMARCA pathway has the potential to deliver a ‘pipeline in a program.’ We are building on our leadership position by advancing the industry’s first highly selective oral SMARCA2 degrader, PRT7732, into the clinic, and will initiate a study of PRT3789 in combination with KEYTRUDA in collaboration with Merck later this year. Additionally, in collaboration with AbCellera, we are developing precision ADCs with SMARCA payloads to extend the reach of our molecules to an even broader set of cancers without SMARCA4 mutations."

"Regarding our clinical development programs, we are very pleased with the progress of both of our SMARCA2 degraders, PRT3789 and PRT7732," added Jane Huang, M.D., President and Chief Medical Officer of Prelude. "We are looking forward to sharing the initial clinical data from the Phase 1 study of our highly selective SMARCA2 degrader which has been chosen as the subject of an oral presentation at the upcoming ESMO (Free ESMO Whitepaper) Congress in September."

Dr. Huang continued, "Additionally, based on the continued progress of PRT2527, our selective CDK9 inhibitor, we intend to present interim phase 1 clinical data, including a potential best-in-class safety profile in the fourth quarter of this year."

Clinical Program Updates and Upcoming Milestones

PRT3789 – A first-in-class, highly selective, intravenous SMARCA2 Degrader

PRT3789 is a first-in-class SMARCA2 degrader, highly selective for SMARCA2 and designed to treat patients with a SMARCA4 mutation. Cancer patients whose tumors have SMARCA4 mutations have a poor prognosis and as a result, this is an area of high unmet medical need.

PRT3789 is in Phase 1 clinical development in biomarker selected SMARCA4 mutant patients. Enrollment remains on track, and the Company expects to conclude monotherapy dose escalation in 2024 and identify a recommended Phase 2 dose. In addition, enrollment of patients into back-fill cohorts enriched for NSCLC and SMARCA4 loss-of-function mutations is ongoing, as is enrollment of the combination with docetaxel cohort.

Objectives for this first Phase 1 clinical trial are to establish the safety and tolerability profile of PRT3789 as both monotherapy and in combination with docetaxel, evaluate activity, pharmacokinetics and pharmacodynamics and determine a dose and potential indications for advancement into registrational clinical trial(s).

Prelude recently launched an educational video series focused on the science of SMARCA biology, the discovery of first-in-class, highly selective SMARCA2 degraders and the unmet medical need for patients with SMARCA4 mutated cancer. This series can be found on the Company’s website under Highly Selective SMARCA2 Degraders – Prelude Therapeutics (preludetx.com).

Interim Phase 1 data selected for an oral presentation at the ESMO (Free ESMO Whitepaper) Congress 2024

The abstract titled "First Clinical Results from a Phase 1 Trial of PRT3789, a First-in-Class Intravenous SMARCA2 Degrader, in Patients with Advanced Solid Tumors with a SMARCA4 Mutation," will be presented by Robin Guo, M.D. from Memorial Sloan Kettering Cancer Center. The ESMO (Free ESMO Whitepaper) Congress 2024 Scientific Committee selected the abstract as an oral presentation.

The presentation is scheduled for September 13th, 2024, at 4:00 PM CEST (10:00 AM EST) in the Santander Auditorium (Hall 5) as part of the Developmental Therapeutics Session.

Abstracts are anticipated to be available on the ESMO (Free ESMO Whitepaper) website on September 9th, 2024 at 12:05 AM CEST (6:05 PM EST on September 8th).

Clinical collaboration announced with Merck to evaluate PRT3789 in combination with KEYTRUDA in patients with SMARCA4-mutated cancers

In July 2024, Prelude announced a clinical collaboration with Merck to evaluate PRT3789 in combination with KEYTRUDA in patients with SMARCA4-mutated cancers.

The mechanistic rationale and pre-clinical data to support the SMARCA2 and anti-PD-1 monoclonal antibody (mAb) combination was previously presented by the Company at the 2023 AACR (Free AACR Whitepaper) AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). In pre-clinical models, SMARCA2 degrader combined with an anti-PD-1 mAb in SMARCA4-mutated cancers enhanced anti-tumor immunity and demonstrated tumor regressions. Please see the Company’s website under Publications – Prelude Therapeutics (preludetx.com) for more information.

Under the terms of the Agreement, Merck will provide KEYTRUDA to Prelude. Prelude will be the sponsor of the Phase 2 clinical combination trial, anticipated to initiate in the fourth quarter of 2024. Prelude and Merck each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

PRT7732 – A potent, highly selective and orally bioavailable SMARCA2 Degrader

Prelude has identified a series of highly selective and orally bioavailable SMARCA2 degraders. The lead oral candidate, PRT7732, recently was granted IND authorization from the FDA and is expected to enter Phase 1 clinical development in the second half of 2024.

PRT2527 – A potent and highly selective CDK9 Inhibitor

PRT2527 is a potent and highly selective CDK9 inhibitor that has the potential to avoid off-target toxicities observed with other less selective CDK9 inhibitors. The Company is currently advancing PRT2527 as monotherapy in both lymphoid and myeloid hematological malignancies, and in combination with zanubrutinib in B-cell malignancies.

PRT2527 is expected to complete monotherapy dose escalation in B-cell malignancies this year. Initiation of dose escalation in myeloid malignancies occurred in the first half of 2024. Interim Phase 1 data is on track for presentation in the fourth quarter of 2024.

Second Quarter 2024 Financial Results 

Cash, Cash Equivalents, and Marketable securities:

Cash, cash equivalents and marketable securities as of June 30, 2024 were $179.8 million. The Company anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude’s operations into 2026. 

Research and Development (R&D) Expenses:

For the second quarter of 2024, R&D expense increased to $29.5 million from $25.0 million for the prior year period. Research and development expenses increased primarily due to an increase in our chemistry, manufacturing, and controls (CMC) expense to support our pre-clinical and clinical research programs. We expect our R&D expenses to vary from quarter to quarter, primarily due to the timing of our clinical development activities.  

General and Administrative (G&A) Expenses:

For the second quarter of 2024, G&A expenses increased to $7.7 million from $7.4 million for the prior year period. The increase is primarily due to an increase in professional fees incurred as we expand our operations to support our research and development efforts.

Net Loss:

For the three months ended June 30, 2024, net loss was $34.7 million, or $0.46 per share compared to $30.4 million, or $0.54 per share, for the prior year period. Included in the net loss for the quarter ended June 30, 2024, was $6.1 million of non-cash expenses related to the impact of expensing share-based payments, including employee stock options, as compared to $6.7 million for the same period in 2023.

On August 12, 2024 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, reported financial results and business updates for the second quarter ended June 30, 2024 (Press release, Adaptimmune, AUG 12, 2024, View Source [SID1234645720]). The Company will host a live webcast at 8:00 a.m. EDT (1:00 p.m. BST) today.

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Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: "On 1 August, we received US FDA approval for Tecelra, the first ever engineered cell therapy for a solid tumor and the first new treatment option for people with synovial sarcoma in more than a decade. We have hit the ground running to make Tecelra available to eligible patients. Patients can start their treatment journey now with healthcare providers able to begin testing and our ordering platform is up and running. Tecelra will be available in 6-10 US authorized treatment centers in the coming weeks. Tecelra is the first product in our sarcoma franchise, and we are planning to commence our rolling BLA submission for lete-cel in 2025 and commercial launch in 2026. We expect our sarcoma franchise to redefine the treatment landscape in advanced soft tissue sarcoma with projected peak US sales of $400 million."

Sarcoma Franchise with Tecelra and lete-cel

● U.S. Food and Drug Administration (FDA) approves Tecelra for the treatment of advanced MAGE-A4+ synovial sarcoma in adults with certain HLA types who have received prior chemotherapy.
● Tecelra is the first engineered cell therapy for solid tumors.
● Tecelra is the first new treatment option for synovial sarcoma in more than a decade.
● Tecelra is a single infusion treatment.
● No Risk Evaluation and Mitigation Strategies (REMS) program was required for BLA approval.
● Patients can start their treatment journey now, with testing approved and available in the United States.
● Sarcoma centers of excellence across the Unites States are being onboarded as Authorized Treatment Centers (ATCs) for Tecelra.
● The approval of Tecelra was based on results of the SPEARHEAD-1 (Cohort 1) trial. The major efficacy outcome was overall response rate (ORR) by independent review and supported by duration of response. Tecelra treatment resulted in an ORR of 43% with a complete response rate of 4.5%. The median duration of response was 6 months (95% CI: 4.6, not reached). Among patients who were responsive to the treatment, 39.0% had a duration of response of 12 months or longer. Data from the pivotal SPEARHEAD-1 trial were previously published in The Lancet earlier this year.

● Data presentations:
o Data from the pivotal IGNYTE-ESO trial of lete-cel (letetresgene autoleucel), an engineered cell therapy targeting NY-ESO-1, in synovial sarcoma (SyS) and myxoid/round cell liposarcoma (MRCLS) was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) annual meeting. The overall response rate (ORR) of 40% was consistent across both SyS and MRCLS, meeting the primary endpoint success criterion for efficacy. Given the trial’s success, Adaptimmune plans to initiate a rolling Biologics License Application (BLA) submission for lete-cel for the treatment of advanced or metastatic MRCLS and synovial sarcoma during 2025. Lete-cel will bolster Adaptimmune’s sarcoma franchise by expanding the addressable patient population to NY-ESO-1 positive MRCLS and SyS solid tumors.
Clinical pipeline

● Adaptimmune recently announced the company had entered into a clinical collaboration agreement with Galapagos to conduct a clinical proof-of-concept trial to evaluate the safety and efficacy of uza-cel (next-generation engineered TCR T-cell therapy, formerly ADP-A2M4CD8) using Galapagos’ decentralized manufacturing platform in patients with head & neck cancer and potential future solid tumor cancer indications.
● Adaptimmune retains the right to develop, manufacture, commercialize, and otherwise exploit uza-cel for platinum-resistant ovarian cancer.
● Uza-cel is being investigated in the SURPASS-3 Phase 2 clinical trial (NCT05601752) for the treatment of platinum-resistant ovarian cancer. Uza-cel received FDA RMAT designation in 2022 for the treatment of patients with platinum resistant ovarian cancer. The SURPASS-3 trial is currently enrolling patients.
● Screening in the SURPASS Phase 1 trial has stopped and enrolment will cease shortly.

Preclinical pipeline

● Wholly owned allogeneic pipeline progressing; process optimization continues at Adaptimmune’s facility in Milton Park, UK.
● IND-enabling activities continue for ADP-600 (PRAME) and ADP-520 (CD70) programs.

Business and corporate updates

● Under the terms of Adaptimmune and Galapagos’ collaboration agreement, Adaptimmune will receive initial payments of $100 million, comprising $70 million upfront and $30 million of R&D funding of which $15m was received on signing, option exercise fees of up to $100 million, additional development and sales milestone payments of up to a maximum of $465 million, plus tiered royalties on net sales.
● Adaptimmune announced in May entry into a Loan and Security Agreement with Hercules Capital, Inc., for a term loan facility of up to $125.0 million. Following the receipt of FDA approval for Tecelra, the Company is eligible to draw down the Tranche 2 Advance of $25.0 million and is in the process of requesting this Tranche 2 Advance.

Financial Results for the three and six months ended June 30, 2024

● Cash / liquidity position: As of June 30, 2024, Adaptimmune had cash and cash equivalents of $211.8 million and Total Liquidity2 of $214.8 million, compared to $144.0 million and $146.9 million respectively, as of December 31, 2023.
● Revenue: Revenue for the three and six months ended June 30, 2024, was $128.2 million and $133.9 million, respectively, compared to $5.1 million and $52.7 million for the same periods in 2023. Revenue has increased in 2024, compared to the same periods in 2023 primarily due to the termination of the Genentech collaboration in the second quarter of 2023, resulting in the majority of the remaining deferred income for the collaboration being recognized as revenue including a cumulative catch-up adjustment of $101.3 million. This was significantly higher than the impact from the termination of the Astellas collaboration in 2023, which resulted in $42.4 million of revenue being recognized in March 2023.
● Research and development (R&D) expenses: R&D expenses for the three and six months ended June 30, 2024, were $40.4 million and $75.7 million, respectively, compared to $30.0 million and $55.5 million for the same periods in 2023. R&D expenses increase due to an increase in the average number of employees engaged in research and development, increases in subcontracted expenditures, an increase in in-process research and development costs and a decrease in offsetting reimbursements receivable for research and development tax and expenditure credits.
● General and administrative (G&A) expenses: G&A expenses for the three and six months ended June 30, 2024, were $19.1 million and $38.8 million, respectively, compared to $20.1 million and $40.5 million for the same periods in 2023. G&A expenses decreased due to restructuring and charges recognised in the first quarter of 2023 that were not repeated in 2024 and an increase in offsetting reimbursements, offset by an increase in other corporate costs due to an increase in accounting, legal and professional fees in the second quarter of 2024 due to fees relating to business development work and preparation for commercialization.
● Net profit/(loss): Net profit attributable to holders of the Company’s ordinary shares for the three and six months ended June 30, 2024, was $69.5 million and $21.0 million, respectively ($0.05 and $0.01 per ordinary share), compared to losses of $21.3 million and $20.4 million ($(0.02) and $(0.02) per ordinary share), for the same periods in 2023.

Today’s Webcast Details

A live webcast and replay can be accessed HERE. Call in information is as follows: +1-844-763-8274 (US or Canada) or +1-647-484-8814 (International). Callers should dial in 5-10 minutes prior to the scheduled start time and simply ask to join the Adaptimmune call.

On August 12, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported that data from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib, a first-in-class menin inhibitor, in adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) have been published in the Journal of Clinical Oncology (Press release, Syndax, AUG 12, 2024, View Source [SID1234645737]).

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"Publication of the pivotal AUGMENT-101 dataset in KMT2Ar acute leukemia allows for a broader dissemination of these important data and highlights revumenib’s impressive and consistent clinical profile that has led to meaningful results for these advanced patients," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "These data serve as the foundation for the NDA filing that is currently being reviewed by the FDA under its RTOR program. As we approach the potential FDA approval of revumenib, we are actively preparing for a successful commercial launch to enable us to deliver this important medicine to patients in need."

"Despite an increased understanding of the mechanisms governing development of KMT2Ar acute leukemia, no available therapies adequately serve this population," said Ghayas C. Issa, M.D., Assistant Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. "The high rate of deep, MRD negative responses along with a safety profile that supports prolonged time on therapy and maintained remission post-stem cell transplant gives me confidence that revumenib could serve as a paradigm-changing treatment."

The FDA has granted Priority Review for the New Drug Application (NDA) for revumenib for the treatment of adult and pediatric R/R KMT2Ar acute leukemia. The NDA is being reviewed under the FDA’s Real-Time Oncology Review Program (RTOR) and has a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2024.

In March 2024, the Company announced the completion of enrollment in the final AUGMENT-101 pivotal trial cohort in patients with R/R mutant nucleophosmin (mNPM1) AML. Topline data is expected in the fourth quarter of 2024 and could support a supplemental NDA filing for revumenib in R/R mNPM1 AML in the first half of 2025.

About the data

The publication entitled "Menin Inhibition With Revumenib for KMT2A-Rearranged Relapsed or Refractory Acute Leukemia (AUGMENT-101)" includes positive data from a total of 94 acute leukemia patients with KMT2Ar in the pivotal trial as of the July 2023 data cutoff, 57 of whom had central confirmation of their KMT2Ar status, sufficient follow-up and were in the efficacy analysis.

The AUGMENT-101 trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the KMT2Ar acute leukemia population. The CR + CRh rate was 23% (10/44; 95% CI: 11.5, 37.8) in adult patients and 23% in pediatric patients (3/13; 95% CI: 5.0, 53.8). The median time to CR + CRh in the overall efficacy-evaluable population was 1.9 months (range: 0.9, 4.6) and the CR + CRh responses were durable with a 6.4-month (95% CI: 3.4, NR) median duration and 46% (6/13) remaining in response at the time of data cutoff. Minimal residual disease (MRD) status was assessed in 10 of the 13 patients who achieved a CR + CRh, 70% (7/10) of whom were MRD negative.

In the efficacy evaluable patients, the overall response rate1 was 63% (36/57; 95% CI: [49.3, 75.6]), and the composite response rate (CRc) was 44% (25/57). MRD status was assessed in 22 of the 25 patients who achieved a CRc, 68% (15/22) of whom were MRD negative. Responses were observed in all major subgroups, including across the number of prior treatments and prior stem cell transplant, and across a broad age range with the youngest responder aged 1 year and oldest aged 75 years. A total of 14 (39%) patients who achieved an overall response underwent HSCT, eight of whom did not achieve a CR or CRh prior to transplant. Half (7/14) of the patients who had an HSCT resumed revumenib treatment post-transplant. Median overall survival at the time of data cutoff was 8.0 months (95% CI: 4.1, 10.9).

Revumenib was well tolerated and the safety profile was consistent with the Company’s previously reported data. In the pivotal AUGMENT-101 trial safety population (n=94), treatment-emergent adverse events (TEAEs) of Grade ≥3 that occurred in ≥10% of patients included febrile neutropenia (37%), neutropenia (29%), thrombocytopenia (21%), anemia (18%), differentiation syndrome (16%), QTc prolongation (14%), sepsis (12%), and hypokalemia (11%). TEAEs leading to dose reduction or discontinuation were low at 9.6% (9/94) and 12.8% (12/94) of patients, respectively. Grade 3 DS was observed in 15% (14/94) of patients while one patient (1%) experienced Grade 4 DS and no patients experienced Grade 5 DS. No Grade 4 or 5 QTc events occurred. There were no discontinuations related to DS, cytopenias or QTc prolongation as of the July 2023 data cutoff.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and full data have now been published in the Journal of Clinical Oncology. Revumenib was granted Orphan Drug Designation for the treatment of AML and ALL by the FDA and for the treatment of AML by the European Commission, and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

On August 12, 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 second quarter ended June 30, 2024, and provided a business update (Press release, Aprea, AUG 12, 2024, View Source [SID1234645721]).

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"Aprea continues to make excellent progress advancing its clinical pipeline of therapeutic candidates," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "We initiated enrollment in the ACESOT-1051 trial, advancing a second clinical asset in our pipeline, APR-1051. APR-1051 is a next-generation inhibitor of WEE1 kinase which has been designed to limit toxicity. Based on its unique characteristics, we believe it could be best in class. We continue to enroll patients in the ABOYA-119 trial evaluating ATRN-119, our ATR inhibitor. We believe that our ongoing progress positions Aprea at the forefront of synthetic lethality drug development. We remain committed to developing new treatments that have a positive impact on the lives of cancer patients while creating value for our shareholders."

Key Business Updates and Potential Upcoming Key Milestones

ACESOT-1051: A Biomarkers Focused, Phase 1 Trial of Oral WEE1 inhibitor, APR-1051, initiated

APR-1051 is a potent and selective small molecule that has been designed to potentially solve liabilities and may achieve greater clinical activity than other WEE1 programs currently in development. Aprea is advancing APR-1051 as monotherapy in cancers with Cyclin E over expression, as well as other biomarkers that are predicted to be sensitive to WEE1 inhibition. Cancers overexpressing Cyclin E represent a high unmet medical need. Patients with Cyclin E overexpression have poor prognosis and, currently, have no effective therapies.
In June 2024, enrollment commenced in the ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) Phase 1 clinical trial evaluating single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. The first patient was dosed at NEXT Oncology, San Antonio, Texas, without any dose-limiting toxicities (including myelosuppression) observed to date in the first cohort. A second patient has been enrolled at The University of Texas MD Anderson Cancer Center and has commenced treatment in the second dose cohort.
The primary objectives of the Phase 1 study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and recommended Phase 2 dose (RP2D); secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective.
The Company will provide an update on the progress of this clinical study by year end. Open-label safety/efficacy data are expected in the first half of 2025.
In June 2024, Aprea hosted a virtual KOL event to discuss APR-1051. Joseph Vacca, Ph.D., Medicinal Chemistry Expert and Consultant to Aprea, discussed the medicinal chemistry history, strategy-guided selective drug design, and preclinical findings of APR-1051. Eric J. Brown, Ph.D., University of Pennsylvania and Consultant to Aprea, discussed preclinical findings across the WEE1 inhibitor class. A replay of the event (with slides) can be accessed on Aprea’s corporate website here.
APR-1051 was featured in two posters at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting which took place in April 2024 in San Diego, which summarized the pre-clinical data supporting APR-1051 and the trial design for ACESOT-1051.
ABOYA-119: Ongoing Clinical Trial Evaluating ATR inhibitor, ATRN-119

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 mutations in DDR-related genes represent a high unmet medical need. Patients with DDR-related gene mutations have a poor prognosis and, currently, have no effective therapies.
ATRN-119 is currently being evaluated in the open-label Phase 1/2a clinical trial of ABOYA-119 (study AR-276-01) as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. The first five dose cohorts (50mg to 550mg once daily) have been completed, and patients continue to enroll in additional cohorts in the dose escalation part of the trial.
The primary endpoint of this Phase 1 trial is the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous, once-daily schedule. Aprea is planning to amend the study protocol to add a group of patients who will receive ATRN-119 twice a day and to investigate the effect of food on ATRN-119 absorption and drug exposure in blood. Under the current protocol, the Company anticipates the ABOYA-119 Phase 1 readout to be available in the first half of 2025.
An update on the ongoing trial was featured in a poster at the AACR (Free AACR Whitepaper) Annual Meeting this past April. A copy of the AACR (Free AACR Whitepaper) poster can be found here.
For more information, please refer to clinicaltrials.gov NCT04905914.
Corporate

Appointed Nadeem Q. Mirza, M.D., M.P.H. as Chief Medical Officer (CMO), effective May 1, 2024. Dr. Mirza had been a consultant to Aprea since February 2023 and has now assumed a more central role in leading the Company’s development of its expanding clinical pipeline.
Select Financial Results for the Second Quarter ended June 30, 2024

As of June 30, 2024, the Company reported cash and cash equivalents of $28.7 million, compared to $21.6 million at December 31, 2023. The Company believes its cash and cash equivalents as of June 30, 2024, will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into the fourth quarter of 2025.
For the quarter ended June 30, 2024, the Company reported an operating loss of $3.8 million, compared to an operating loss of $3.7 million in the comparable period in 2023.
Grant revenue, primarily from the National Cancer Institute of the National Institutes of Health ("NIH") for the three months ended June 30, 2024, and 2023 was approximately $0.6 million and $0.2 million, respectively.
Research and development expenses were approximately $2.6 million for the quarter ended June 30, 2024, compared to approximately $2.2 million for the comparable period in 2023. The increase was primarily due to an increase in expenses related to the initiation of ACESOT-1051, our Phase 1 dose-escalation study evaluating APR-1051, our small molecule WEE1 inhibitor, in the second quarter of 2024.
General and administrative expenses were approximately $1.9 million for the quarter ended June 30, 2024, compared to approximately $1.7 million for the comparable period in 2023. The increase was primarily related to an increase in personnel costs primarily related to severance expense.
The Company reported a net loss of $3.5 million ($0.58 per basic share) on approximately 5.9 million weighted-average common shares outstanding for the quarter ended June 30, 2024, compared to a net loss of $3.3 million ($0.87 per basic share) on approximately 3.7 million weighted average common shares outstanding for the comparable period in 2023.