On August 7, 2024 Allakos Inc. (the "Company") (Nasdaq: ALLK), a biotechnology company developing antibodies for the treatment of allergic, inflammatory and proliferative diseases, reported a business update and announced financial results for the second quarter ended June 30, 2024 (Press release, Allakos, AUG 7, 2024, View Source [SID1234645486]).

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Recent Allakos Events

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Initiated the randomized, double-blind, placebo-controlled Phase 1 trial of intravenous (IV) AK006 in patients with chronic spontaneous urticaria.
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Completed dosing in the randomized, double-blind, placebo-controlled subcutaneous (SC) AK006 cohort in healthy volunteers.
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Reported safety, pharmacokinetics (PK), and pharmacodynamic (PD) results from the Phase 1 trial of IV AK006 in healthy volunteers.
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Presented preclinical data at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress on mast cell inhibition with AK006.

Upcoming Allakos Anticipated Milestones

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Report safety, PK, and PD results from the Phase 1 trial of SC AK006 in healthy volunteers in Q3 2024.
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Report randomized double-blind, placebo-controlled data from the Phase 1 trial of AK006 in patients with CSU at year end 2024.

Cash Guidance

Allakos ended the second quarter of 2024 with $123.1 million in cash, cash equivalents and investments. Allakos’ financial outlook, restructuring activities and estimated cash runway as reported by the Company in January 2024 remain unchanged. The Company reiterates that the restructuring activities will extend the cash runway into mid-2026 and continues to expect to end 2024 with total cash, cash equivalents and investments in the range of $81 to $86 million. The Company reiterates that an estimated $30 million of closeout, severance and other costs will be paid in 2024 in connection with exiting the lirentelimab development program, of which we have spent $13 million to date in the first six months of 2024. Approximately $1 million of these payments were made in the second quarter of 2024.

Second Quarter 2024 Financial Results

Allakos ended the second quarter of 2024 with $123.1 million in cash, cash equivalents and investments resulting in a net decrease in cash, cash equivalents and investments of $16.2 million during the second quarter of 2024.

Research and development expenses were $19.4 million in the second quarter of 2024 compared to $27.3 million in the second quarter of 2023, a decrease of $7.9 million. This quarter over quarter decrease is attributed to $2.5 million of lower contract research and development costs, primarily due to halting lirentelimab development, $2.5 million of decreased compensation costs and a $2.9 million decrease in other research and development expenses.

General and administrative expenses were $9.2 million for the second quarter of 2024 compared to $10.5 million for the second quarter of 2023, a decrease of $1.3 million. The quarter over quarter change included $0.7 million of decreased compensation costs and $0.6 million of decreased other general and administrative expenses.

Allakos reported a net loss of $26.7 million in the second quarter of 2024 compared to $35.1 million in the second quarter of 2023. Net loss per basic and diluted share was $0.30 for the second quarter of 2024 compared to $0.41 in the second quarter of 2023.

On August 7, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported its financial results for the quarter ended June 30, 2024, and provided an update on corporate progress (Press release, Revolution Medicines, AUG 7, 2024, View Source [SID1234645502]).

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The company continues making progress on its 2024 development priorities:

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Advancing its RAS(ON) multi-selective inhibitor RMC-6236 into monotherapy pivotal trials.
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Pancreatic cancer: The company recently provided updated data on the clinical safety, tolerability and antitumor activity in patients with pancreatic ductal adenocarcinoma (PDAC) from its ongoing RMC-6236 monotherapy study. Strong preliminary progression-free survival (PFS) and overall survival (OS) PDAC data support the company’s plans to initiate a pivotal, randomized, controlled Phase 3 monotherapy study in the second-line (2L) treatment of patients with metastatic PDAC this year; work is underway toward this goal.
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Lung cancer: Data from the RMC-6236 monotherapy study in patients with non-small cell lung cancer (NSCLC) continue to mature. The company remains on track to initiate a pivotal study in previously-treated patients with RAS-mutated NSCLC this year.

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Expanding the reach of RMC-6236 monotherapy and/or combinations into earlier lines of therapy. Based on compelling preliminary monotherapy data in 2L PDAC, the company plans to evaluate RMC-6236 in earlier lines of treatment for pancreatic cancer including the first-line, locally advanced, and resectable settings. In addition to monotherapy, the company is currently evaluating RMC-6236 in combination with chemotherapy, which is the current standard of care for patients with PDAC.

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Qualifying its RAS(ON) mutant-selective inhibitors, RMC-6291 (G12C-selective inhibitor) and RMC-9805 (G12D-selective inhibitor), for late-stage development.
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With the goal of moving RMC-6291 into early lines of therapy in NSCLC, the company is currently evaluating the RAS(ON) inhibitor doublet of RMC-6291 with RMC-6236 as well as RMC-6291 with pembrolizumab.
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This doublet approach was recently highlighted in the Cancer Discovery publication that demonstrated robust antitumor activity by a RAS(ON) multi-selective inhibitor in combination with a RAS(ON) G12C-selective inhibitor in preclinical models of refractory KRAS G12X NSCLC.

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The company continues to enroll patients with solid tumors harboring KRAS G12D mutations in the RMC-9805 monotherapy study.

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In support of its continuing pipeline momentum and commercial ambitions, the company appointed Frank Clyburn to its board of directors; Mr. Clyburn is a distinguished executive who led Merck’s global Keytruda franchise from its inception and helped establish Merck as a global leader in oncology. The company also expanded its senior management group with key new hires in medical affairs, corporate affairs, drug safety and program leadership.

"Confidence in our RAS(ON) inhibitor platform and assets continues to grow and has been bolstered particularly by the strength of the interim safety, PFS and OS data shown in July for patients with pancreatic cancer in the RMC-6236 monotherapy study. Based on current benchmarks for first- and second-line treatment of metastatic PDAC, we believe RMC-6236 has the potential to become an important new therapeutic option to address large unmet medical needs for patients with this threatening disease," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "The appointment of Frank Clyburn to our board of directors and several strategic additions to our executive team support our deep focus on enabling the next stage of growth and maturation for Revolution Medicines. We have made substantial progress in planning for the initiation of our first pivotal, Phase 3 study for RMC-6236 in pancreatic cancer, and are working actively to prepare to advance RMC-6236 into earlier lines of therapy."

Clinical Development Highlights

Plans to Advance RMC-6236 Monotherapy into Pivotal Trials

Pancreatic cancer: On July 15, 2024, the company reported updated data on the clinical safety, tolerability and antitumor activity from its ongoing monotherapy study evaluating RMC-6236 in patients with previously treated metastatic PDAC across dose cohorts ranging from 160 mg daily to 300 mg daily as of a May 11, 2024 data cutoff date. Key findings included:

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A total of 127 patients treated were evaluated for safety and tolerability.
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Approximately 22 percent of these patients experienced a Grade 3 or higher treatment-related adverse event (TRAE), and 96 percent of these patients experienced a TRAE of any grade.
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The most common TRAEs observed were rash and gastrointestinal-related toxicities. Reported TRAEs led to dose modifications (dose interruption and/or reduction) in 28 percent of these patients and there were no discontinuations due to TRAEs.
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The company also reported preliminary PFS and OS data in 2L treatment of patients with metastatic PDAC.
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The median PFS for patients with KRAS G12X mutations (n=42) was 8.1 months (95% confidence interval (CI); 5.9 months – not-estimable (NE)) and for patients with any RAS mutation (G12X, G13X and Q61X) (n=56) was 7.6 months (95% CI; 5.3 months – NE).
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For patients with KRAS G12X mutations and those with any RAS mutation, the observed OS was not estimable (95% CI for both groups; 8.5 months, NE).
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Based on initial feedback from the U.S. Food and Drug Administration, including supportive discussions on high-level trial design including a 300 mg daily dose, the company expects to initiate its Phase 3 registrational trial in the 2L treatment of patients with metastatic PDAC, called RASolute 302, this year.

Lung cancer: The company expects to share updated NSCLC data from its ongoing RMC-6236 monotherapy study in the fourth quarter of 2024 and to launch a registrational study to evaluate RMC-6236 in previously-treated patients with advanced NSCLC in the fourth quarter of 2024.

Evaluating RMC-6236 in Earlier Lines of Therapy

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PDAC. Evaluation is ongoing for RMC-6236 in combination with standard of care chemotherapy in first-line PDAC.

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NSCLC. Evaluation is ongoing for RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with advanced RAS-mutated NSCLC. The company expects to disclose initial clinical pharmacokinetic (PK), safety, tolerability and antitumor activity data for the combination of RMC-6236 with pembrolizumab in the fourth quarter of 2024.

Qualifying RMC-6291 for Late-Stage Development

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Combination Development. Evaluation of RMC-6291 with RMC-6236 and RMC-6291 with pembrolizumab, with or without chemotherapy, is ongoing. The company expects to disclose initial clinical PK, safety, tolerability and antitumor activity data for the combination of RMC-6291 with RMC-6236 in the fourth quarter of 2024 and for the combination RMC-6291 with pembrolizumab in the first half of 2025.

Qualifying RMC-9805 for Late-Stage Development

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Monotherapy Development. The company expects to disclose initial clinical PK, safety, tolerability and antitumor activity data for RMC-9805 in the fourth quarter of 2024.

RAS Innovation Engine

Beyond the first wave of clinical-stage RAS(ON) inhibitors, additional clinical development opportunities include the RAS(ON) mutant-selective inhibitors RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C) and the RAS companion inhibitors RMC-4630 (SHP2) and RMC-5552 (mTORC1/4EBP1).

On August 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 June 30, 2024 (Press release, Allogene, AUG 7, 2024, View Source [SID1234645487]).

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"The second quarter has been an excellent example of the power of momentum, particularly as we bring into the fold community cancer centers who are eager to be a part of our pivotal Phase 2 ALPHA3 trial and we are now manufacturing all of our CAR T investigational products in-house," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "Beyond the progress we’ve seen across our four core programs with cema-cel in blood cancers, ALLO-329 in autoimmune disease, and ALLO-316 in relapsed and refractory renal cell carcinoma, there is renewed energy from investigators, clinical trial sites, and top-tier investors as it becomes increasingly apparent that we have the potential to reshape the future of CAR T therapies."

Program Updates

Cema-Cel: Pivotal ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL)
The pivotal Phase 2 ALPHA3 trial was initiated in June 2024 and site activation is ahead of schedule with ten community cancer and academic centers opened in less than two months. Patient screening for minimal residual disease (MRD) and enrollment are proceeding as planned.

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 the Foresight CLARITY Investigational Use Only (IUO) MRD test, powered by PhasED-Seq. 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 YE 2026. A potential biologics license application (BLA) submission is targeted for 2027.

Cema-Cel: Phase 1 Trial in Chronic Lymphocytic Leukemia (CLL)
Enrollment is ongoing in the relapsed/refractory (r/r) CLL cohort of the Phase 1 ALPHA2 trial of cema-cel. Initial data readout from the CLL cohort is projected by early 2025.

ALLO-329: CD19/CD70 Dual CAR with Dagger Technology in Autoimmune Disease (AID)
ALLO-329, the Company’s first CRISPR-based AlloCAR T investigational product for AID, incorporates the Dagger technology, which is intended to reduce or eliminate the need for lymphodepletion while targeting CD19+ B-cells and CD70+ activated T-cells, both of which are likely to play a role in AID. 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)
A Phase 1 data update from approximately 20 patients with CD70 positive RCC, which will include details on the diagnostic and treatment algorithm used to mitigate treatment-associated hyperinflammatory response seen in some patients, is planned by YE 2024. 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.

2024 Second Quarter Financial Results
•Research and development expenses were $50.4 million for the second quarter of 2024, which includes $5.3 million of non-cash stock-based compensation expense.
•General and administrative expenses were $16.1 million for the second quarter of 2024, which includes $8.2 million of non-cash stock-based compensation expense.
•Net loss for the second quarter of 2024 was $66.4 million, or $0.35 per share, including non-cash stock-based compensation expense of $13.6 million and $5.0 million in non-cash impairment of long-lived asset expense.
•The Company had $444.6 million in cash, cash equivalents, and investments as of June 30, 2024.

Based on the cash runway as of June 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 PM PT/5:00 PM ET 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 August 7, 2024 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported financial results for the second quarter of 2024 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, AUG 7, 2024, View Source [SID1234645503]).

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"We are very pleased with the continued strong momentum of our U.S. launch of OGSIVEO for adults with desmoid tumors. In the second quarter, we also completed the submission of our NDA for mirdametinib in NF1-PN, which positions us to potentially have our second medicine available for patients in 2025," said Saqib Islam, Chief Executive Officer of SpringWorks. "Our focus for the second half of 2024 will be to drive broader adoption of OGSIVEO, to advance our commercial preparations for the launch of mirdametinib for children and adults with NF1-PN, to continue advancing OGSIVEO and mirdametinib through the European regulatory process, and to progress our emerging portfolio for patient populations with high unmet needs."

Recent Business Highlights and Upcoming Milestones

OGSIVEO (Nirogacestat)

Strong commercial execution of the OGSIVEO launch, with net product revenue of $40.2 million in the second quarter of 2024.
In May 2024, SpringWorks introduced OGSIVEO 150 mg and 100 mg tablets in blister packaging, which was developed to enhance patient convenience with OGSIVEO.
A Marketing Authorization Application (MAA) for nirogacestat for the treatment of adult patients with desmoid tumors is under review with the European Medicines Agency (EMA).
Additional data from the Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors highlighting consistent safety and efficacy across subgroups of high-risk patient populations and updated ovarian toxicity resolution data supporting the transience of ovarian toxicity were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
SpringWorks expects to present long-term follow-up data from the Phase 3 DeFi trial at a medical conference in the second half of 2024.
SpringWorks expects to report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with recurrent ovarian granulosa cell tumors in the second half of 2024.
SpringWorks is continuing to support several industry and academic collaborator studies evaluating nirogacestat as part of B-cell maturation antigen (BCMA) combination therapy regimens across treatment lines in patients with multiple myeloma.
Mirdametinib

SpringWorks completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib for the treatment of children and adults with NF1-PN.
The Company expects to complete the submission of an MAA for mirdametinib for the treatment of children and adults with NF1-PN in the European Union in the second half of 2024.
Data from the pediatric and adult cohorts of the Phase 2b ReNeu trial were presented in an oral presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting and were also featured at the 2024 Global NF Conference and at the International Symposium on Pediatric Neuro-Oncology (ISPNO) 2024 meeting. Results showed robust objective response rates confirmed by blinded independent central review, deep responses, significant reductions in pain, improvement in other quality of life measures, and a manageable and tolerable safety profile were achieved across both the pediatric and adult cohorts. SpringWorks expects to publish the ReNeu trial results in a peer-reviewed journal in the second half of 2024.
A poster evaluating the dispersible tablet of mirdametinib in children with NF1-PN in the ReNeu trial was presented at the ISPNO 2024 meeting. Patients and caregivers reported high acceptability scores for ease of swallowing and willingness to take the dispersible tablet formulation, indicating that this formulation provides an acceptable option for children or adults with swallowing difficulties.
Initial data from the Phase 1/2 trial evaluating mirdametinib in patients with pediatric low-grade gliomas (pLGG) were presented at the ISPNO 2024 meeting. Results from 23 patients enrolled in the Phase 1 portion of the study suggested that mirdametinib, which has high blood brain barrier penetration, has encouraging clinical activity in patients with recurrent/progressive pLGG across a variety of MAPK pathway aberrations. The Phase 2 portion of the study is ongoing and recruiting patients.
Emerging Pipeline

A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the first half of 2025. Brimarafenib is an investigational, selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, Ltd.
Patients continue to be enrolled in several combination therapy oncology programs: a Phase 1/2a study of brimarafenib and mirdametinib in MAPK mutant solid tumors, a Phase 1b trial of brimarafenib and Amgen’s EGFR inhibitor, panitumumab, in colorectal and pancreatic cancer patients with known MAPK pathway mutations, and a Phase 1b trial of mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with NRAS mutant solid tumors.
SpringWorks initiated a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024.
General Corporate

In July, SpringWorks appointed Martin Mackay, Ph.D. to the Company’s Board of Directors. Dr. Mackay is a highly accomplished R&D executive with more than 30 years of pharmaceutical and biotech R&D experience, including leadership roles at Pfizer, AstraZeneca and Alexion.
Second Quarter 2024 Financial Results

Product Revenue: OGSIVEO net product revenue was $40.2 million in the second quarter of 2024.
Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $57.8 million for the second quarter of 2024, compared to $47.0 million for the comparable period of 2023. The increase in SG&A expense was primarily attributable to commercial activities supporting the U.S. launch of OGSIVEO, as well as commercial readiness activities to support the U.S. launch of mirdametinib, if approved.
Research and Development (R&D) Expenses: R&D expenses were $44.4 million for the second quarter of 2024, compared to $35.9 million for the comparable period of 2023. The increase in R&D expenses was primarily attributable to an increase in costs related to drug manufacturing, clinical trials, other research, consulting and professional services, and an increase in employee costs associated with headcount growth.
Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $39.9 million, or $0.54 per share, for the second quarter of 2024. This compares to a net loss of $77.9 million, or $1.25 per share, for the comparable period of 2023.
Cash, Cash Equivalents, and Marketable Securities: Cash, cash equivalents and marketable securities were $521.9 million as of June 30, 2024.
Conference Call Information

SpringWorks will host a conference call and webcast today, Wednesday, August 7, at 8:30 a.m. ET to review its second quarter 2024 financial results and discuss recent business updates. To join the live webcast and view the corresponding slides, please click here. To access the live call by phone, please pre-register for the call by clicking here. Once registration is complete, participants will be provided with a dial-in number and conference code to access the call. A replay of the webcast will be available for a limited time following the event on the Investors and Media section of the Company’s website at View Source

On August 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 second quarter ended June 30, 2024 (Press release, Applied Therapeutics, AUG 7, 2024, View Source [SID1234645488]).

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"Momentum continues with our steady regulatory progress in Classic Galactosemia and SORD Deficiency," said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. "We are incredibly pleased to share our alignment with the Neurology Division of the FDA regarding a potential second NDA submission for govorestat for the treatment of SORD Deficiency. Both Galactosemia and SORD Deficiency are rare neurological diseases with no currently approved treatment options. At Applied, we are dedicated to creating transformative treatments for rare diseases, and we continue to work closely with regulatory agencies and patient advocacy groups to ensure that treatments become available for patients with these debilitating diseases."

Recent Highlights

· Govorestat PDUFA Target Action Date of November 28, 2024; MAA under CHMP Review by EMA; Updated Cognition Data Included in Review. In the process of preparing for the United States Food and Drug Administration (FDA) inspection, it was discovered that the vendor hired to compile NIH Toolbox data for the Company used an adult formula for calculation of about one third of composite cognition and motor skills scores. Adjusting the formula to the pediatric formula resulted in significantly improved data for cognition as compared to the prior data, demonstrating improvement in the govorestat (AT-007) treated group of approximately 8 points on a standard scale, which was statistically significant compared to placebo (p=0.032). This also resulted in a statistically significant effect on the primary endpoint sensitivity analysis which included cognition (p=0.034). The motor skills data did not change substantially. These updates were disclosed and discussed with the FDA and European Medicines Agency (EMA) and will be used in the ongoing evaluation of the New Drug Application (NDA) and Marketing Authorization Application (MAA). As previously announced, the FDA Prescription Drug User Fee Act (PDUFA) target action date is 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 MAA for govorestat for the treatment of Classic Galactosemia to the EMA, which was validated in December 2023 and is under review by the EMA’s Committee for Medicinal Products for Human Use (CHMP). As previously announced, in April 2024, the EMA granted a 3-month extension to the Day 120 clock stop period to allow sufficient time for responses to the CHMP’s Day 120 list of questions. 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.

· FDA Advisory Committee Meeting to Review Govorestat NDA for the Treatment of Classic Galactosemia Tentatively Scheduled for October 9, 2024. The FDA notified the Company of their tentative plans to convene the Genetic Metabolic Diseases Advisory Committee (GeMDAC) on October 9, 2024, to discuss the Company’s NDA for govorestat for the treatment of Classic Galactosemia. The date is tentative and has not yet been confirmed in the federal register. The newly formed GeMDAC will consist of experts in the fields of medical genetics, inborn errors of metabolism, epidemiology, and other related specialties.

· Company Aligned with the Neurology I Division of the FDA on Potential Submission of an NDA for Govorestat for the Treatment of SORD Deficiency Under Accelerated Approval. In July 2024, the Company held a Type C meeting with the FDA to align on the regulatory path forward for govorestat for the treatment of SORD Deficiency. The Neurology I Division confirmed that the data generated to-date was appropriate for a potential NDA submission under the FDA’s Accelerated Approval Program, and discussed the design of a new confirmatory study to be completed as a post-marketing requirement. The Company plans to hold a pre-NDA meeting to discuss administrative aspects of the submission in the second half of this year, and expects to submit an NDA early in the first quarter of 2025. 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 INSPIRE study will be offered open-label govorestat treatment and will be followed for additional safety data generation. The review and potential approval of govorestat for SORD is independent of the ongoing review of govorestat for Classic Galactosemia.

· APLT Added to Russell 3000 Index. In June 2024, as part of the Russell indexes annual reconstitution, the Company was added to the Russell 3000 Index, a market capitalization-weighted equity index that tracks the performance of the largest 3,000 U.S. stocks. Membership of the Russell indexes is primarily determined by objective, market-capitalization rankings and style attributes. Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies.

· Participated in Multiple Medical and Patient Advocacy Group Focused Conferences. In the second and third quarters of 2024, the Company deepened its relationships and partnership with the patient community, presenting data and giving keynote addresses at the following medical meetings and patient advocacy group conferences:

o Hereditary Neuropathy Foundation (HNF) Charcot-Marie Tooth Syndrome (CMT) Summit, June 7-8 in San Diego, California;
o Charcot-Marie-Tooth Associate (CMTA) Strategy to Accelerate Research (STAR) Advisory Board meeting held June 21 in Montreal, Canada;
o Peripheral Nerve Society (PNS) 2024 Annual Meeting, held June 22-25 in Montreal, Canada;
o Sponsored and presented at the 2024 Galactosemia Foundation Conference, held July 18-20 in Concord, North Carolina.

Financial Results

· Cash and cash equivalents and short-term investments totaled $122.2 million as of June 30, 2024, compared with $49.9 million at December 31, 2023.

· Research and development expenses for the three months ended June 30, 2024, were $10.0 million, compared to $11.9 million for the three months ended June 30, 2023. The decrease of approximately $1.9 million was primarily related to decreased expenses associated with clinical and pre-clinical expenses for the near completion of AT-001 and AT-007 and drug manufacturing and formulation costs, partially offset by an increase in regulatory and personnel expenses.

· General and administrative expenses were $10.6 million for the three months ended June 30, 2024, compared to $5.3 million for the three months ended June 30, 2023. The increase of approximately $5.3 million was primarily related to an increase in legal and professional fees of $1.3 million, an increase in commercial expenses to support planned commercialization of govorestat of $3.5 million, and an increase in personnel expenses of $1.1 million due to increased headcount and salary increases, offset by a decrease in stock-based compensation, insurance expenses and other miscellaneous expense.

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Net income for the second quarter of 2024 was $2.9 million, or $0.02 per basic common share and a net loss of $0.13 per diluted common share, compared to a net loss of $29.6 million, or $0.37 per basic and diluted common share, for the second quarter of 2023.

· Cash runway: The Company expects that its cash and cash equivalents will fund the business into 2026. Additionally, the Company expects that the sale of the priority review voucher (PRV), which would be granted upon a potential NDA approval of govorestat for the treatment of Galactosemia, could substantially extend the Company’s cash runway.