On November 7, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results and recent highlights for the third quarter ended September 30, 2024 (Press release, Cardiff Oncology, NOV 7, 2024, View Source [SID1234647923]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This quarter has been exciting as our Phase 2 clinical trial in second-line KRAS-mutant mCRC was published in one of the most esteemed medical journals in the field of oncology, Journal of Clinical Oncology. Our findings demonstrated that onvansertib combined with FOLFIRI/bev was well-tolerated, and revealed a 7.7x greater clinical benefit in bev naïve patients compared to patients who were previously treated with bev," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "We believe the results of our JCO publication validate our ongoing CRDF-004 trial evaluating onvansertib + chemo for the treatment of mCRC in the first-line setting, where all patients are bev naïve. Furthermore, we are pleased with the progress we have made in the trial as we leverage Pfizer’s resources and capabilities, and are grateful for the commitment from the patients and investigators at our trial sites across the U.S. As of today, the trial continues to generate patient data that will allow us to provide an initial data release by the end of the year. Overall, we are optimistic about onvansertib’s potential to become a meaningful treatment option for the 50,000 new patients diagnosed with RAS-mutated mCRC in the U.S. every year who have not had access to any new treatment options in several decades."

Upcoming expected milestones

•
First-line RAS-mutated metastatic colorectal cancer (mCRC) randomized initial data readout from the CRDF-004 trial expected by end of 2024

Company highlights for the quarter ended September 30, 2024 and subsequent weeks include:

•
Published clinical data of the combination of onvansertib with FOLFIRI and bev in second-line KRAS mutant mCRC in the peer-reviewed Journal of Clinical Oncology, the flagship publication of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)
•
Phase 2 clinical trial treating patients with KRAS-mutant mCRC (NCT03829410) demonstrated that onvansertib combined with FOLFIRI and bev was well-tolerated, and exhibited clinical activity in the second-line setting.
•
A post hoc analysis revealed a greater clinical benefit in bev naïve patients, who demonstrated an ORR of 77% and mPFS of 14.9 months compared to an ORR of 10% and mPFS of 6.6 months in those previously exposed to bev.

•
Published promising preclinical data demonstrating the combination of onvansertib and alpelisib in PIK3CA-mutated HR-positive breast cancer resistant to palbociclib and endocrine therapy in the peer-reviewed journal, Cancers
•
The combination of onvansertib and alpelisib synergistically inhibited cell viability, suppressed PI3K signaling, and induced G2/M arrest and apoptosis in PI3K-activated cell lines.
•
The combination demonstrated superior anti-tumor activity compared to the single agents in three PDX models.
•
Pharmacodynamic studies confirmed inhibition of both PLK1 and PI3K activity and pronounced apoptosis in the combination-treated tumors.
•
The findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA-mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation.
Third Quarter 2024 Financial Results

Liquidity, cash burn, and cash runway

As of September 30, 2024, Cardiff Oncology had approximately $57.7 million in cash, cash equivalents, and short-term investments.

Net cash used in operating activities for the third quarter of 2024 was approximately $10.5 million, an increase of approximately $2.5 million from $8.0 million for the same period in 2023.

Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations into Q1 2026.

Operating results

Total operating expenses were approximately $12.8 million for the three months ended September 30, 2024, an increase of $1.8 million from $11.0 million for the same period in 2023. The increase in operating expenses was primarily due to clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib.

On November 7, 2024 Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported business updates and reported financial results for the third quarter of 2024 (Press release, Boundless Bio, NOV 7, 2024, View Source [SID1234647922]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The third quarter was marked by steady execution across the portfolio, with the POTENTIATE and STARMAP trials continuing to enroll patients," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "In September, together with our development partner, SOPHiA GENETICS, we presented analytical validation for our proprietary ecDNA diagnostic, ECHO, a critical first step in identifying ecDNA positive patients for our clinical programs. We are capitalized to advance our lead programs through proof-of-concept data and remain focused on delivering impactful results for our patients and stakeholders."

Program Highlights and Upcoming Milestones

BBI-355, a novel, oral, potent, selective CHK1 inhibitor targeting replication stress for cancer patients with driver oncogene amplifications

•
Enrollment is proceeding in the Phase 1/2 POTENTIATE clinical trial evaluating BBI-355 as a single agent and in combination with targeted therapies in patients with oncogene amplified solid tumors.
•
No new safety signals have been observed.
•
The company anticipates reporting initial clinical proof-of-concept data in the second half of 2025.

BBI-825, a novel, oral, potent, selective RNR inhibitor targeting ecDNA assembly and repair for cancer patients with resistance oncogene amplifications

•
Enrollment continues to progress in the single agent, dose-escalation portion of the STARMAP clinical trial, with initial clinical proof-of-concept data expected in the second half of 2025.

ecDTx 3, a novel kinesin program involved in ecDNA segregation

•
The company’s third ecDTx program, directed to a previously undrugged kinesin target essential for ecDNA segregation whose inhibition is synthetic lethal to ecDNA-enabled cancer cells, continues to advance through lead optimization.

ECHO, a proprietary diagnostic for detection of ecDNA amplified oncogenes

•
In September, analytical validation data was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress for the company’s proprietary ecDNA diagnostic ECHO (ecDNA Harboring Oncogenes). ECHO is currently being used as a clinical trial assay to determine ecDNA status of patients enrolled in the BBI-355 POTENTIATE trial.

Third Quarter 2024 Financial Results

•
Cash Position: Cash, cash equivalents, and short-term investments totaled $167.1 million as of September 30, 2024.
•
R&D Expenses: Research and development (R&D) expenses were $14.1 million for the third quarter of 2024 compared to $11.6 million for the same period in 2023.
•
G&A Expenses: General and administrative (G&A) expenses were $4.6 million for the third quarter of 2024 compared to $3.3 million for the same period in 2023.
•
Net Loss: Net loss totaled $16.5 million for the third quarter of 2024 compared to $13.2 million for the same period in 2023.

About BBI-355

Boundless Bio’s lead ecDNA-directed therapy (ecDTx), BBI-355, is a novel, oral, selective small molecule inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial (NCT05827614) in cancer patients with oncogene amplifications. CHK1 is a master regulator of cells’ response to replication stress (RS). RS is elevated in cancer cells with oncogene amplification, including on ecDNA, and, because of this, represents a key vulnerability of those cells. BBI-355 was designed to exploit the elevated RS in ecDNA-enabled oncogene amplified cancer cells by disrupting proper CHK1 function in regulating RS and thereby facilitating catastrophic RS to preferentially kill cancer cells relative to healthy cells.

About BBI-825

Boundless Bio’s second ecDTx, BBI-825, is a novel, oral, selective small molecule inhibitor of ribonucleotide reductase (RNR) being studied in the ongoing, first-in-human, Phase 1/2 STARMAP clinical trial (NCT06299761) in colorectal cancer patients with BRAFV600E or KRASG12C mutations and resistance gene amplifications. In preclinical studies, BBI-825 demonstrated low double digit nanomolar RNR inhibition and tumor growth inhibition, including regressions, in both the prevention and treatment of amplification-mediated resistance in mitogen-activated protein kinase (MAPK) pathway-activated tumors. RNR is the rate-limiting enzyme responsible for cellular de novo synthesis of deoxynucleotide triphosphates (dNTPs), the building blocks of DNA, and is essential to the assembly and repair of ecDNA. BBI-825 was shown to dysregulate ecDNA-reliant cancer cell dNTP pools, deplete ecDNA, and was synthetic lethal in multiple oncogene amplified preclinical cancer models.

On November 7, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, reported positive results from its Phase 1/2 dose escalation and cohort expansion study of AU-007 (Press release, Aulos Bioscience, NOV 7, 2024, View Source [SID1234647921]). The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting in Houston, Texas.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Preliminary Phase 2 data reveal that a combination of AU-007 and low-dose, subcutaneous aldesleukin is clinically active in melanoma, a finding consistent with Phase 1 data demonstrating clinical activity in a range of patients whose tumors had progressed through prior checkpoint inhibitors. Data from all 77 patients show durable reductions in immunosuppressive Treg cells – a result unprecedented in the IL-2 class – with a correlation between longer progression-free survival outcomes as Treg reduction deepens.

"We believe these data represent preliminary clinical proof of concept for our unique monoclonal antibody, AU-007, and we are confident in its emerging profile as a potential best-in-class therapeutic," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "We look forward to presenting a fuller and more mature set of Phase 2 data for melanoma, renal cell carcinoma and non-small cell lung cancer in the first half of next year."

Key findings from preliminary results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 77 patients as of the data cutoff date of September 28, 2024, are as follows:

A tolerable and manageable safety profile was observed at all doses evaluated in Phase 1 dose escalation.

No dose-limiting toxicity occurred throughout Phase 1 dose escalation.
Most drug-related adverse events were Grade 1 or 2 except for:
Grade 3 anemia in one patient who entered the study with Grade 2 anemia, had rapid disease progression and received only two doses of the study drug.
Grade 4 cytokine release syndrome (CRS) in one patient that resolved with steroids, IV fluids and brief vascular pressor support, and did not require tocilizumab. This patient was noted retrospectively to have subclinical elevated IL-6 (5x upper limit of normal) serum levels, likely due to an active case of gout at baseline.
Transient Grade 3 elevated lipase in one patient that was not associated with clinical symptoms and resolved without intervention.
Transient (3-7 days) Grade 3 or 4 lymphopenias in six patients. The lymphopenias were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue.
Strong evidence of anti-tumor activity was observed in heavily pre-treated patients, particularly in melanoma.

Two patients with melanoma refractory to prior anti-CTLA-4 and anti-PD-1 therapy were treated with AU-007 every two weeks (Q2W) and one administration of low-dose, subcutaneous aldesleukin (recombinant human IL-2), and experienced deep and durable tumor shrinkages of 48% and 100% in target lesions.
One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 Q2W and one loading dose of subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control.
Anti-tumor activity was also observed in heavily pre-treated patients with renal cell carcinoma (RCC), bladder cancer, head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) whose tumors had progressed through checkpoint inhibitors.
AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the IL-2 class.

A decrease in Tregs appears to be a critical determinant of observed efficacy, with greater median decreases observed in patients receiving one loading dose of low-dose, subcutaneous aldesleukin compared to low-dose, subcutaneous aldesleukin administered Q2W. Based on the Treg reduction levels and other PD findings, the company has made the decision to use the loading dose rather than the Q2W schedule of subcutaneous aldesleukin going forward.
Greater decreases in Tregs on treatment is associated with longer progression-free survival (PFS) across the Phase 1 and Phase 2 portions of the AU-007 trial. Patients with a Treg cell reduction greater than the median of 43% had longer PFS outcomes than those with a Treg cell reduction less than the median of 43%.
The Phase 2 expansion cohorts evaluating AU-007 and low-dose, subcutaneous aldesleukin continue to enroll patients, with a focus on melanoma and non-small cell lung cancer. An additional Phase 2 cohort will evaluate AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor; anti-PD-L1) in NSCLC. The company anticipates presenting updated clinical data in the first half of 2025.

The poster, "A phase 1/2 dose escalation and cohort expansion study of AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin in advanced solid tumors," (Abstract 685) is available to meeting registrants as an electronic poster on the SITC (Free SITC Whitepaper) 2024 virtual meeting platform. It will be presented in a poster session on Friday, November 8, 2024, 9:00 a.m.-7:00 p.m. CST in Exhibit Halls AB.

The poster presentation is also available on the Aulos Bioscience website in the Abstracts and Publications section.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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

•
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.

•
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.

•
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

•
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.
•
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.
•
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.
•
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.