On November 7, 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 third quarter ended September 30, 2024, and provided a business update (Press release, Aprea, NOV 7, 2024, View Source [SID1234647920]).

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"We continue to make meaningful progress advancing our pipeline of two clinical stage therapeutic candidates as well as strengthening our clinical team," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "We are ahead of schedule with the enrollment of the Phase 1 ACESOT-1051 trial evaluating our next generation WEE1 inhibitor, APR-1051. Preliminary results at subtherapeutic doses demonstrate the product to be well-tolerated with no unexpected toxicities. APR-1051 has been designed to limit off target toxicity and, based on its unique characteristics, we believe it will be best-in-class. Active enrollment is also ongoing in the Phase 1/2a ABOYA-119 study evaluating ATRN-119, our first-in-class macrocyclic ATR inhibitor. To optimize dosing and scheduling we added a twice-daily dosing regimen."

Key Business Updates and Potential Upcoming Key Milestones

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

APR-1051 is a potent and selective small molecule that has been designed to potentially solve tolerability challenges of the class 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 may predict sensitivity to WEE1 inhibition. 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 available.
Enrollment is ongoing 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 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; pharmacodynamic parameters are exploratory objectives.
In October 2024, preliminary findings from the ACESOT-1051 trial were reported in a poster at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics, in Barcelona, Spain. As of October 7, 2024, three patients were enrolled (sub-therapeutic doses of 10 mg, 20 mg and 30 mg) in the first three Cohorts with data available on two of these patients. Preliminary results to date have demonstrated that APR-1051 is well-tolerated with no unexpected toxicities. The poster can be viewed on Aprea’s corporate website here.
Cohort 3 has been cleared ahead of schedule, with no safety concerns noted. Accelerated titration is complete and, in November 2024, the trial begun enrolling at Cohort 4 (50 mg) within the BOIN (Bayesian Optimal Interval) design.
Preliminary efficacy data from ACESOT-1051 are expected in the first half of 2025. For more information, refer to ClinicalTrials.gov NCT06260514.
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, there are no effective therapies available for them.
ATRN-119 is currently being evaluated in the open-label Phase 1/2a clinical trial of ABOYA-119 as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. The primary endpoint of this Phase 1 trial is the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous schedule.
An update from ABOYA-119 was provided in a poster at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics on October 25, 2024. Patients are currently being enrolled at dose level 6 (800mg once daily) in the dose escalation part of the trial. As of October 2, 2024, 14 of 20 patients experienced adverse events (AEs) considered to be possibly/probably related to ATRN-119. No related SAE or grade 4-5 AEs have been observed. No signs of hematological toxicity have been registered and no DLTs have been observed to date. Preliminary signs of clinical benefit were observed in two patients treated at the 50 mg and 200 mg dose level. A copy of the poster can be viewed here.
In order to optimize dosing and scheduling early in the development process, a protocol amendment has been submitted to add dose level 9 (1500 mg once daily) and twice-daily (400mg to 750mg) dosing. The addition of twice-daily dosing is supported by the pharmacodynamic properties of the drug and the favorite safety profile observed to date. The dose escalation for the once-daily and the twice-daily schedules will be studied independently. Under the current updated protocol, the Company anticipates the ABOYA-119 Phase 1 readout to be available in the second half of 2025.
For more information, please refer to clinicaltrials.gov NCT04905914.
Corporate

In October 2024, the Company engaged Philippe Pultar, MD as senior medical advisor to support the development and advancement of APR-1051. Dr. Pultar is a seasoned pharmaceutical executive with extensive experience in oncology. He was most recently employed at Zentalis Pharmaceuticals where he played a key role in the strategy and execution of the global clinical development of azenosertib, a WEE1 inhibitor.
Select Financial Results for the third quarter ended September 30, 2024

As of September 30, 2024, the Company reported cash and cash equivalents of $26.2 million, compared to $21.6 million at December 31, 2023. The Company believes its cash and cash equivalents as of September 30, 2024, will be sufficient to fund the Company’s operating expenses and capital expenditure requirements through at least twelve months from the date of issuance of the condensed consolidated financial statements on Form 10-Q for the quarter ended September 30, 2024.

For the quarter ended September 30, 2024, the Company reported an operating loss of $4.1 million, compared to an operating loss of $3.5 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 September 30, 2024 and 2023 was approximately $0.4 million and $0.3 million, respectively.
Research and development expenses for the three months ended September 30, 2024 were approximately $2.8 million, compared to approximately $2.1 million for the three months ended September 30, 2023. The overall increase was primarily due to an increase in costs related to the ABOYA-119 clinical trial to evaluate ATRN-119 and personnel costs. These were offset in part by a decrease in costs related to IND enabling studies for ATRN-1051.
General and administrative expenses for the three months ended September 30, 2024 were approximately $1.6 million, compared to approximately $1.7 million for the three months ended September 30, 2023. The decrease was primarily related to a decrease in insurance costs.
The Company reported a net loss of $3.8 million ($0.64 per basic share) on approximately 5.9 million weighted-average common shares outstanding for the quarter ended September 30, 2024, compared to a net loss of $3.2 million ($0.86 per basic share) on approximately 3.7 million weighted average common shares outstanding for the comparable period in 2023.

On November 7, 2024 Applied Therapeutics, Inc. (Nasdaq: APLT) (the "Company"), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, reported financial results for the third quarter ended September 30, 2024 (Press release, Applied Therapeutics, NOV 7, 2024, View Source [SID1234647919]).

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"We are proud of the significant progress we’ve made this quarter as we prepare for a transformational year ahead, with a focus on transitioning from a clinical-stage company to a commercial organization. With regulatory submissions for govorestat underway in two rare disease indications of urgent unmet need, Classic Galactosemia and SORD Deficiency, we continue to thoughtfully execute our pre-launch initiatives," said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. "As we approach the final stages of the NDA review process for Classic Galactosemia in parallel with a near-term NDA submission for SORD Deficiency, we remain confident in the promise of govorestat and its ability to address the underlying mechanisms of both diseases. We look forward to the opportunity to bring govorestat to patients in 2025."

Recent Highlights

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NDA Review of Govorestat for the Treatment of Classic Galactosemia Ongoing with PDUFA Target Action Date of November 28, 2024; MAA under CHMP Review by EMA. The New Drug Application (NDA) review of govorestat for the treatment of Classic Galactosemia remains ongoing within the U.S. Food and Drug Administration (FDA)’s Division of Rare Diseases and Medical Genetics with a Prescription Drug User Fee Act (PDUFA) target action date of November 28, 2024. Govorestat was previously granted Pediatric Rare Disease designation and will qualify for a Priority Review Voucher (PRV) upon approval. The Company has also submitted a Marketing Authorization Application (MAA) for govorestat for the treatment of Classic Galactosemia to the European Medicines Agency (EMA), which was validated in December 2023 and remains under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP). The review remains within the Day 120 clock stop period and the Company expects a decision by the EMA early in the first quarter of 2025. The NDA and MAA submission packages are supported by rapid and sustained reduction in galactitol, which resulted in a meaningful benefit on clinical outcomes across pediatric patients, alongside a favorable safety profile. The submission packages include clinical outcomes data from the Phase 3 registrational ACTION-Galactosemia Kids study in children aged 2-17 with Galactosemia, the Phase 1/2 ACTION-Galactosemia study in adult patients with Galactosemia, and preclinical data. If approved, govorestat would be the first medication indicated for the treatment of Galactosemia and would be Applied Therapeutics’ first commercial product.

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NDA Submission Under Accelerated Approval for Govorestat for the Treatment of SORD Deficiency Anticipated in Early Q1 2025. Following a Type C meeting with the Neurology I Division of the FDA to align on the regulatory path forward for govorestat for the treatment of SORD Deficiency, the Company expects to submit an NDA early in the first quarter of 2025. The review and potential approval of govorestat for the treatment of SORD is independent of the ongoing review of govorestat for Classic Galactosemia. If govorestat is approved for the treatment of Classic Galactosemia, the regulatory submission for the treatment of SORD will be submitted as a supplementary New Drug Application (sNDA). Patients in the Phase 3 INSPIRE study have been transitioned to open-label govorestat treatment and will be followed for additional safety data generation.

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Highlighted Clinical Data and Development Characterization of Govorestat for the Treatment of Classic Galactosemia at Medical Conferences. In the third and fourth quarters of 2024, the Company presented at the 2024 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and the American Society of Human Genetics (ASHG) Annual Meeting 2024. The presentations highlighted the mechanism of disease pathogenesis for Classic Galactosemia, the design of the first clinical outcomes study in Classic Galactosemia and the results of the ACTION-Galactosemia Kids study.

Financial Results

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Cash and cash equivalents and short-term investments totaled $98.9 million as of September 30, 2024, compared with $49.9 million at December 31, 2023.
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Research and development expenses for the three months ended September 30, 2024, were $14.8 million, compared to $10.8 million for the three months ended September 30, 2023. The increase of approximately $4.0 million was primarily related to an increase in clinical, pre-clinical and regulatory expense related to govorestat, an increase in drug manufacturing and formulation costs related to the release of legacy accruals in prior year that did occur in current year, and an overall increase in personnel and stock-based compensation expenses.
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General and administrative expenses were $15.0 million for the three months ended September 30, 2024, compared to $4.7 million for the three months ended September 30, 2023. The increase of approximately $10.3 million was primarily related to an increase in legal and professional fees of $1.7 million, an increase in commercial expenses to support planned commercialization of govorestat of $6.8 million, an increase in personnel and stock-based compensation expenses of $1.4 million due to increased headcount, and an increase in other miscellaneous expense of $0.5 million due to an overall increase in data storage costs to support planned commercialization, offset by a decrease in insurance expenses.
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Net loss for the third quarter of 2024 was $68.6 million, or $0.48 per basic and diluted common share, compared to a net loss of $42.4 million, or $0.47 per basic and diluted common share, for the third quarter 2023.

On November 7, 2024 ALX Oncology Holdings Inc., ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer in new ways and extend patients’ lives, reported financial results for the third quarter ended September 30, 2024, and provided a corporate update (Press release, ALX Oncology, NOV 7, 2024, View Source [SID1234647918]).

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"We made substantial clinical progress during the third quarter, most notably announcing topline data from our ASPEN-06 Phase 2 trial in which our lead candidate evorpacept became the first and only CD47-blocking agent to show a durable clinical benefit and a well-tolerated safety profile in a prospective randomized clinical trial," said Jason Lettmann, Chief Executive Officer of ALX Oncology. "These results provided further validation for evorpacept’s novel mechanism of action and our robust evorpacept clinical program. We anticipate achieving several additional clinical milestones in the near-term that could advance evorpacept towards being a best-in-class, combinable therapeutic across a wide range of cancer types."

Third Quarter 2024 Highlights and Recent Developments

Reported topline data results in July from the multi-center, international ASPEN-06 Phase 2 clinical trial (NCT05002127) evaluating evorpacept in combination with HERCEPTIN (trastuzumab), CYRAMZA (ramucirumab) and paclitaxel (Evo-TRP) against trastuzumab, CYRAMZA (ramucirumab) and paclitaxel (TRP) for the treatment of patients with HER2-positive gastric/gastroesophageal junction (GEJ) cancer, where all patients had received an anti-HER2 agent in prior lines of therapy.
Evorpacept improved tumor response in patients with HER2-positive gastric/GEJ cancer, becoming the first CD47 blocker to show promising and durable response with a well-tolerated safety profile in a prospective randomized study.
Evo-TRP achieved a confirmed overall response rate (ORR) of 40.3% compared to 26.6% for the TRP control arm and demonstrated a median duration of response of 15.7 months compared to 7.6 months in the intent to treat population (ITT) (N=127). The primary analysis of the ITT compared Evo-TRP to an assumed RP control ORR of 30% Secondary endpoints of PFS and OS were immature at the time of analysis.
Evo-TRP combination showed the greatest response with an ORR of 54.8% compared to 23.1% in the TRP control arm in a pre-specified population of patients with fresh HER2-positive biopsies (n=48).
In September, commenced patient dosing to investigate evorpacept plus SARCLISA (isatuximab-irfc) and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM) in the Sanofi-partnered arm of the randomized UMBRELLA phase 1/2 clinical study.
Sanofi is conducting the two-part multicenter, randomized, open-label, controlled, parallel-group study (NCT04643002) to evaluate the safety, efficacy, pharmacokinetics and biomarker data of evorpacept in combination with SARCLISA and dexamethasone in patients with RRMM.
Part 1 is evaluating the dosing of evorpacept in combination with standard doses of SARCLISA and dexamethasone to identify a recommended evorpacept dose.
Part 2 is investigating the efficacy and safety of this three-drug combination in an expanded population of patients with RRMM.
In August, enhanced the leadership team by appointing Alan Sandler, M.D. to Board of Directors, a distinguished leader in oncology and drug development with over 30 years of experience across industry and academia.
Dr. Sandler’s industry background includes serving as Executive Vice President, Chief Medical Officer at Mirati Therapeutics, prior to its acquisition by Bristol Myers Squibb. Before joining Mirati, he served as President, Global Head of Development in Oncology at Zai Lab, and prior to that, he was the Senior Vice President and Global Head, Product Development of Oncology Solid Tumors at Genentech, a member of the Roche Group.
Presented at the 2024 Cantor Fitzgerald Global Healthcare Conference in New York City in September.
Participated in fireside chat with Analyst, Li Watsek and conducted investor meetings.
Upcoming Clinical Milestones for Evorpacept’s Development Pipeline

Breast Cancer – Results from a Phase 1b/2 combination trial evaluating evorpacept in combination with Jazz Pharmaceuticals’ zanidatamab in HER2-positive and HER2-low metastatic breast cancer will be presented at a poster spotlight presentation at the San Antonio Breast Cancer Symposium on December 12, 2024
Gastric/GEJ Cancer – Updated results of ASPEN-06 Phase 2 clinical trial (1H 2025)
Head and Neck Squamous Cell Carcinoma – Topline results from a Phase 2 randomized clinical trial of ASPEN-03 with KEYTRUDA (pembrolizumab) (1H 2025)
Head and Neck Squamous Cell Carcinoma – Topline results from a Phase 2 randomized clinical trial of ASPEN-04 with KEYTRUDA and chemotherapy (1H 2025)
Urothelial Cancer – Updated results from a Phase 1 clinical trial of ASPEN-07 in combination with PADCEV (enfortumab vedotin) (1H 2025)
Gastric/GEJ Cancer – Initiation of Phase 3 registrational randomized clinical trial for evorpacept (mid-2025)
Breast Cancer – Topline results from a Phase 1b I-SPY TRIAL with ENHERTU (fam-trastuzumab deruxtecan-nxki) (2H 2025)
Third Quarter 2024 Financial Results:

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments as of September 30, 2024, were $162.6 million. The Company believes its cash, cash equivalents and investments, which includes the proceeds from sales under its at-the-market ("ATM") offering in the first half of 2024 are sufficient to fund planned operations well into Q1 2026.
Research and Development ("R&D") Expenses: R&D expenses consist primarily of pre-clinical, clinical and manufacturing expenses related to the development of the Company’s current lead product candidate, evorpacept, and R&D employee-related expenses. These expenses for the three months ended September 30, 2024, were $26.5 million, compared to $45.8 million for the prior-year period. R&D expenses decreased by $19.3 million during the three months ended September 30, 2024, compared to the three months ended September 30, 2023. Lower expense was primarily attributable to a decrease of $22.2 million in clinical and development costs primarily due to manufacturing of clinical trial materials to support active clinical trials for our lead product candidate, evorpacept, slightly offset by increased preclinical costs for development of new targets, an increase in personnel and related costs, and an increase in stock-based compensation expense.
General and Administrative ("G&A") Expenses: G&A expenses consist primarily of administrative employee-related expenses, legal and other professional fees, patent filing and maintenance fees, and insurance. These expenses for the three months ended September 30, 2024, were $6.1 million, compared to $7.5 million for the prior year period. G&A expenses decreased by $1.4 million during the three months ended September 30, 2024, compared to the three months ended September 30, 2023. The decrease was primarily attributable to lower stock-based compensation expense and lower accounting consulting costs.
Net loss: GAAP net loss was $30.7 million for the three months ended September 30, 2024, or ($0.58) per basic and diluted share, as compared to a GAAP net loss of $51.0 million for the three months ended September 30, 2023, or ($1.24) per basic and diluted share. Non-GAAP net loss was $23.7 million for the three months ended September 30, 2024, as compared to a non-GAAP net loss of $44.0 million for the three months ended September 30, 2023. A reconciliation of GAAP to non-GAAP financial results can be found at the end of this news release.

On November 7, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported corporate updates and announced financial results for the quarter ended September 30, 2024 (Press release, Allogene, NOV 7, 2024, View Source [SID1234647917]).

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"We are proud of the progress made in the third quarter of 2024 to advance our investigational allogeneic cell products in key "firsts" – our first-line consolidation trial in large B-cell lymphoma with cema-cel, ALLO-316 as the first allogeneic CAR T product candidate to demonstrate positive results in solid tumors, and the first CD19/CD70 dual CAR T candidate specifically designed for autoimmune disease," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "We believe these efforts have the potential to redefine treatment paradigms, tailoring therapies to meet the unique needs of large patient populations, and enabling broader real-world adoption. Allogene remains dedicated to driving innovation that improves outcomes for patients with both cancer and autoimmune diseases."

Program Updates

Cema-Cel: Pivotal ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL)
The pivotal Phase 2 ALPHA3 trial is the main focus for the Company. The trial was initiated in June 2024 and now has almost 30 sites activated and screening for patients with minimal residual disease (MRD).

This groundbreaking study is evaluating the use of cemacabtagene ansegedleucel (cema-cel) as part of the first line (1L) treatment regimen for patients with LBCL who are likely to relapse after standard 1L treatment. ALPHA3 is the first pivotal trial to offer CAR T as part of 1L treatment consolidation.

This innovative ALPHA3 trial will identify patients at high risk for relapse after 1L treatment by utilizing Foresight CLARITY powered by PhasED-Seq, a novel and highly accurate Investigational Use Only (IUO) test for MRD. This randomized trial will enroll approximately 240 patients and is designed to demonstrate a meaningful improvement in event free survival (EFS) in patients treated with cema-cel relative to patients who receive the current standard of care (observation). ALPHA3 is expected to complete enrollment in 1H 2026. Efficacy analyses are expected to occur in 2026 and will include an interim EFS analysis monitored by the independent Data Safety Monitoring Board (DSMB) in 1H 2026 and the data readout of the primary EFS analysis by YE 2026. A potential biologics license application (BLA) submission is targeted for 2027.

ALLO-329: CD19/CD70 Dual CAR with Dagger Technology in Autoimmune Disease (AID)
The Company will present pre-clinical data for its next-generation investigational AlloCAR T candidate for autoimmune indications, ALLO-329, at the American College of Rheumatology’s annual meeting, ACR Convergence 2024, November 18, 2024, in Washington, D.C.

ALLO-329 offers a novel approach to treating autoimmune diseases as the first allogeneic CD19/CD70 dual CAR T product specifically designed to target CD19+ B-cells and CD70+ activated T-cells, both of which are key players in autoimmune diseases. The investigational product utilizes CRISPR-based site-specific integration and incorporates the Company’s clinically validated Dagger technology, which aims to reduce or eliminate the need for lymphodepletion, believed to be a potentially significant obstacle to the wider adoption of CAR T therapies in autoimmune applications.

The Company plans to file an investigational new drug (IND) application in Q1 2025 and expects to have proof-of-concept by YE 2025.

ALLO-316: TRAVERSE Trial in Renal Cell Carcinoma (RCC)
The Company will present an update to the ongoing Phase 1 TRAVERSE trial in an oral presentation at the 2024 International Kidney Cancer Symposium (IKCS, November 8, 2024) and at a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting (November 9, 2024). The trial evaluates ALLO-316, the Company’s first AlloCAR T product candidate for the treatment of solid tumors. The Phase 1 TRAVERSE trial is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy. These presentations highlight strong evidence of anti-tumor activity of ALLO-316 following standard FC (fludarabine (30 mg/m2) and cyclophosphamide (500 mg/m2)) lymphodepletion in patients with CD70 positive RCC tumors.

As of the October 14, 2024 data cutoff, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was five days. Data from dose escalation cohorts as well as a newly opened Phase 1b expansion cohort are included in the presentations. The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC lymphodepletion.

Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate (ORR) of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score (TPS) of ≥50% who received the Phase 1b expansion regimen. Patients with a TPS of ≥50% comprise the majority of patients with advanced or metastatic RCC. Of those with a TPS ≥50, 76% (16/21) experienced a reduction in tumor burden. Two of six (33%) patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at ≥4 months.

The most common all-grade adverse events were cytokine release syndrome (CRS) (with only one grade ≥3), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%), and nausea (51%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was minimal at 8% and no graft-versus-host disease (GvHD) occurred.

Two dose limiting toxicity (DLT) events of autoimmune hepatitis and cardiogenic shock were reported. Each event occurred in two separate participants who received FCA (FC plus ALLO-647) lymphodepletion and DL2 of ALLO-316. Three Grade 5 treatment-related adverse events were reported: 1) cardiogenic shock, which was one of the two DLT events; 2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316 – this participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation; and 3) failure to thrive in a participant 16 months after treatment with ALLO-316 – this subject had tumor response of stable disease (SD) at month 12 and no interval scans to evaluate disease status prior to death.

On October 29, 2024, the Company announced that it had received Regenerative Medicine Advanced Therapy (RMAT) designation for ALLO-316 for adult patients with advanced or metastatic RCC. The RMAT designation was based on Phase 1 clinical data from the TRAVERSE trial indicating the potential of ALLO-316 to address the unmet need for patients with difficult-to-treat RCC who have failed multiple standard RCC therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.

2024 Third Quarter Financial Results

Research and development expenses were $44.7 million for the third quarter of 2024, which includes $5.6 million of non-cash stock-based compensation expense.
General and administrative expenses were $16.3 million for the third quarter of 2024, which includes $7.8 million of non-cash stock-based compensation expense.
Net loss for the third quarter of 2024 was $66.3 million, or $0.32 per share, including non-cash stock-based compensation expense of $13.4 million and $10.7 million in non-cash impairment of long-lived asset expense.
The Company had $403.4 million in cash, cash equivalents, and investments as of September 30, 2024.
Based on its cash, cash equivalents and investments as of September 30, 2024, the Company continues to expect its cash runway to fund operations into the second half of 2026. Guidance remains unchanged from the most recent update with an expectation of a decrease in cash, cash equivalents, and investments of approximately $200 million in 2024. GAAP Operating Expenses are expected to be approximately $300 million, including estimated non-cash stock-based compensation expense of approximately $60 million. These estimates exclude any impact from potential business development activities.

Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

On November 7, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported that it will concurrently present new data from the Phase 1 TRAVERSE trial in an oral presentation at the 2024 International Kidney Cancer Symposium (IKCS) and a poster session at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Allogene, NOV 7, 2024, View Source [SID1234647916]). The trial evaluates ALLO-316, the Company’s first AlloCAR T product candidate for the potential treatment of solid tumors. The ongoing Phase 1 TRAVERSE trial is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed following treatment with an immune checkpoint inhibitor and VEGF-targeting therapy. These presentations highlight compelling evidence of CAR T activity and anti-tumor efficacy in 26 patients with RCC tumors known to be CD70 positive who were evaluable for efficacy outcomes.

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"ALLO-316, the leading "off-the-shelf" CAR T product candidate currently in development for solid tumors, continues to show remarkable potency in the TRAVERSE trial. Data from the Phase 1 study demonstrating significant anti-tumor activity in patients with metastatic disease resistant to multiple therapeutic classes, even with standard lymphodepletion, potentially marks a major advancement in the field," said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. "The unprecedented cell expansion and persistence driven by CD70 CAR-intrinsic Dagger technology, along with strong evidence of tumor infiltration by CAR T cells, highlights the distinctive features of ALLO-316. We believe these findings from our Phase 1 trial lay the groundwork for a new generation of allogeneic cell therapies."

As of the October 14, 2024 data cutoff, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes. The median time from enrollment to the start of therapy was five days. Data from dose escalation cohorts and ongoing Phase 1b expansion cohort are included in the presentations. The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC500 (fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/d) for 3 days) lymphodepletion regimen. The Phase 1b expansion cohort is expected to ultimately include approximately 20 patients. Additional data from the Phase 1b expansion cohort is expected to be announced in mid-2025.

Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate (ORR) of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score (TPS) of ≥50% who received DL2. Patients with a TPS of ≥50% comprise the majority of patients with advanced or metastatic RCC. Of those with a TPS ≥50, 76% (16/21) experienced a reduction in tumor burden. Two of six (33%) patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at ≥4 months.

Response Rates by CD70 Status and Dose

Patients Evaluable for Disease Outcomesa (N=34)
CD70 Positive (N=26)

CD70 Negative
or Unknown
(N=8)
All
(N=26) FCAb
(N=8) FCc
(N=18) DL2 FC500
(Phase 1b)
(N=8)
Best overall response,d n/N (%)
High TPS (≥50)
Low TPS (<50) 7/26 (27)
7/21 (33)
0/5 (0) 1/8 (13)
1/6 (17)
0/2 (0) 6/18 (33)
6/15 (40)
0/3 (0) 3/8 (38)
3/6 (50)
0/2 (0) 0/8 (0)
NA
NA
Confirmed ORR,e n/N (%)
High TPS (≥50)
Low TPS (<50) 5/26 (19)
5/21 (24)
0/5 (0) 1/8 (13)
1/6 (17)
0/2 (0) 4/18 (22)
4/15 (27)
0/3 (0) 2/8 (25)
2/6 (33)
0/2 (0) 0/8 (0)
NA
NA
aPatients evaluable for disease outcome includes those who received ALLO-316 and had at least one tumor assessment.
bStandard fludarabine and cyclophosphamide plus ALLO-647
cIncludes FC300 and FC500
dBest overall response across visits did not require confirmation for CR/PR.
eConfirmed overall response of CR/PR required confirmation at the subsequent visit.

The most common all-grade adverse events were cytokine release syndrome (CRS) (with only one grade ≥3), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%) and nausea (51%). Immune effector cell-associated neurotoxicity syndrome (ICANS) was minimal at 8% and no graft-versus-host disease (GvHD) occurred.

Safety: Most Prevalent TEAEs (>40% Any Grade Incidence) and AESI

Adverse Event, n (%) All Patients (N=39) DL2 FC500 (N=11)
All Grades Grade ≥3 All Grades Grade ≥3
Any TEAE 39 (100) 29 (81) 11 (100) 8 (73)
CRS 24 (62) 1 (3) 8 (73) 0
Fatigue 23 (59) 1 (3) 2 (18) 0
Neutropenia 22 (56) 20 (51) 7 (64) 7 (64)
White blood cell count decreased 21/(54) 19 (49) 8 (73) 8 (73)
Anemia 20 (51) 13 (33) 7 (64) 5 (46)
Nausea 20 (51) 0 3 (27) 0
Thrombocytopenia 18 (46) 10 (26) 7 (64) 3 (27)
Pyrexia 16 (41) 2 (5) 4 (36) 0
AEs of Special Interest Any Grade Grade ≥3 Any Grade Grade ≥3
Infectiona
Viral infections 24 (62)
13 (33) 12 (31)
2 (5) 5 (46)
2 (18) 2 (18)
0
Neurotoxicityb
Headache 17 (44)
8 (21) 12 (31)
2 (5) 5 (46)
2 (18) 2 (18)
0
IEC-HS 5 (13) 1 (3) 2 (18) 0
ICANS 3 (8) 0 3 (27) 0
Graft-versus-host disease 0 0 0 0
TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first. IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH. Two patients developed an inflammatory syndrome prior to the existence of IEC-HS as a term in MedDRA, which has been updated as of September 2023.
aInfection events (62%) were primarily low grade; the most common was viral infections (33%) with cytomegalovirus infection and COVID-19 (any grade, 18% and 15%; Grade ≥3, 0% and 5%, respectively).
bNeurotoxicity includes system organ class of nerve system disorders and psychiatric disorders with onset date up to Study Day 30 post ALLO-316 infusion.

Two DLT events of autoimmune hepatitis and cardiogenic shock were reported. Each event occurred in 2 separate participants who received FCA (FC300 plus ALLO-647) lymphodepletion and DL2 of ALLO-316. Three Grade 5 treatment-related adverse events were reported: 1) cardiogenic shock, which was one of the 2 DLT events; 2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316. This participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation; 3) failure to thrive in a participant 16 months after treatment with ALLO-316. This subject had tumor response of stable disease (SD) at month 12 and no interval scans to evaluate disease status prior to death.

About ALLO-316 (TRAVERSE)
ALLO-316 is an AlloCAR T investigational product targeting CD70, which is highly expressed in renal cell carcinoma (RCC). CD70 is also selectively expressed in several cancers, creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. The ongoing Phase 1 TRAVERSE trial is designed to evaluate the safety, tolerability, and activity of ALLO-316 in patients with advanced or metastatic clear cell RCC. In October 2024 the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation based on the potential of ALLO-316 to address the unmet need for patients with advanced or metastatic RCC. The FDA previously granted Fast Track Designation (FTD) to ALLO-316 in March 2023. In April 2024, the Company announced a $15 million award from the California Institute for Regenerative Medicine (CIRM) to support the ongoing TRAVERSE trial with ALLO-316 in RCC.