On August 12, 2024 Theralase Technologies Inc. ("Theralase" or the "Company") (TSXV: TLT) (OTCQB: TLTFF), a clinical stage pharmaceutical company dedicated to the research and development of light and/or radiation activated small molecules for the safe and effective destruction of various cancers, bacteria and viruses reported the Company’s unaudited condensed consolidated interim financial statements for the six-month period ended June 30, 2024. ("Financial Statements") (Press release, Theralase, AUG 12, 2024, View Source [SID1234645739]).

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Theralase will be hosting a conference call on Wednesday August 21st, 2024 at 11:00 am ET, which will include a presentation of the financial and operational results for the six-month period ended June 30, 2024. Questions are welcome. To ensure Theralase has time to review and properly address them during the call, please send them in advance to [email protected].

Zoom Meeting Link: View Source

Conference Call in: 1-647-558-0588 (Canada) / 1-646-558-8656 (US) – not required for those attending by Zoom.

An archived version will be available on the website following the conference call.

Financial Summary:

For the six-month period ended June 30th:

1 Other represents foreign exchange, interest accretion on lease liabilities and / or interest income

Financial Highlights

For the six-month period ended June 30, 2024;

Total revenue decreased 35%, year over year.
Cost of sales was $186,324 (67% of revenue) resulting in a gross margin of $90,077 (33% of revenue). In comparison, the cost of sales for the same period in 2023 was $224,947 (53% of revenue) resulting in a gross margin of $201,140 (47% of revenue). The gross margin decrease, as a percentage of sales year over year, is attributed to an increase in material costs.
$145,915, from $147,304 for the same period in 2023, a 1% decrease.
The decrease is a result of reduced spending on general and administrative expenses (59%) and stock-based compensation (28%) (due to the cumulative effect of accounting for the vesting of stock options granted in the current and previous years).
for the Drug Division decreased to $1,368,333 from $1,594,676 for the same period in 2023, a 10% decrease. The decrease is primarily attributed to a decrease in costs for Study II patient enrollment and treatment.
The increase is attributed to development of a new software program for the TLC-2000 Cool Laser Therapy system.
Net loss was $2,400,461, which included $374,445 of net non-cash expenses (i.e.: amortization, stock-based compensation expense and foreign exchange gain/loss). This compared to a net loss in 2023 of $2,564,187, a 6% year-over-year reduction, which included $474,558 of net non-cash expenses. The Drug Division represented $1,938,024 of this loss (81%). The decrease in net loss is primarily attributed to decreased spending on research and development expenses in Study II.
Operational Highlights:

Non-Brokered Private Placement:

On February 5, 2024, the Company closed a non-brokered private placement of units. On closing, the Company issued an aggregate of 6,666,670 units at a price of $CAN 0.18 per Unit for aggregate gross proceeds of approximately $CAN 1,200,000 of which 1,310,502 units were purchased by certain insiders of the Corporation, representing gross proceeds of $235,890. Each Unit consisted of one common share of the Company and one non-transferable warrant. Each Warrant entitles the holder to acquire an additional Common Share at a price of $CAN 0.25 for a period of 5 years following the date of issuance.

On April 24, 2024, the Company closed a non-brokered private placement of units. On closing, the Company issued an aggregate of 4,167,778 units at a price of $0.18 per Unit for aggregate gross proceeds of approximately $750,200. Each Unit consisted of one common share of the Company and one non-transferable common share purchase warrant. Each Warrant entitles the holder to acquire an additional Common Share at a price of $0.25 for a period of 5 years following the date of issuance.

On July 8, 2024, the Company closed a non-brokered private placement of units. On closing, the Company issued an aggregate of 3,522,729 units at a price of $0.22 per Unit for aggregate gross proceeds of approximately $775,000. Each Unit consisted of one common share of the Company and one non-transferable common share purchase warrant. Each Warrant entitles the holder to acquire an additional Common Share at a price of $0.30 for a period of 5 years following the date of issuance.

In 2024, the Company plans to secure funding through various equity and debt instruments to allow the Company the ability to become base shelf eligible. This will allow the Company sufficient funding to complete enrollment into Study II by year end, data lock in mid 2026 and position the Company for FDA and Health Canada approval by the end of 2026, subject to achieving FDA Priority Review."

Study II Update:

On February 8th, 2024, Dr. Michael Jewett joined the Company in the role of an independent consultant, to assist the Company in the accruement of patients into Study II. Under the terms of the consulting agreement, Dr. Jewett will be responsible for working with existing clinical study sites and helping to onboard new clinical study sites to assist Theralase to complete enrollment and provide the primary study treatment to 75 to 100 patients in Study II, preferably by December 31, 2024.

To date, Theralase has enrolled and treated 72 patients in Study II, who have been provided the primary Study II Procedure. The clinical study sites have screened an additional 3 patients, who they are planning to enroll and treat over the next 4 to 6 weeks, bringing the total to 75 treated patients.

Theralase plans to add up to 5 new CSSs in 2024, as well as increase enrollment at the existing 10 Clinical Study Sites ("CSSs") to complete Study II accruement by the end of 2024 / beginning of 2025.

90% (65/72) of treated patients have been evaluated at the 90 days assessment visit for treatment safety and efficacy according to the clinical study protocol.

For the primary endpoint of Study II (Complete Response ("CR") at any point in time) 63% (41/65) of treated patients achieved a CR.

For the secondary endpoint of Study II (duration of CR) 44% (18/41) of treated patients, who achieved a CR, maintained their CR response for at least 12 months.

For the tertiary endpoint of Study II (safety of Study Procedure) 100% (65/65) experienced no Serious Adverse Events ("SAEs") directly related to the Study Drug or Study Device.

Break Through Designation Update:

In 2020, the FDA granted Theralase Fast Track Designation ("FTD") for Study II. As a Fast Track designee, Theralase has access to early and frequent communications with the FDA to discuss Theralase’s development plans and ensure the timely collection of clinical data to support the approval process. The accelerated communication with the FDA potentially allows, the Study Procedure, to be the first intravesical, patient-specific, light-activated, Ruthenium-based small molecule for the treatment of patients diagnosed with BCG-Unresponsive NMIBC CIS, (with or without recurrent / resected papillary Ta/T1 tumours). FTD can also lead to Break Through Designation ("BTD"), Accelerated Approval ("AA") and/or Priority Review, if certain criteria are met, which the FDA previously defined to the Company for BTD as clinical data on approximately 20 to 25 patients enrolled and provided the primary Study Procedure, who demonstrate significant safety and efficacy clinical outcomes.

To this list, the FDA has added: Post Study II Monitoring of Response and Central Pathology Laboratory Review.

The Company is currently working with the CSSs, a biostatistics organization and a regulatory organization to update the pre-BTD submission with clinical data clarifications, identified by the FDA. The Company plans to resubmit the pre-BTD submission to the FDA in 3Q2024 for FDA review of these clarifications. Once the pre-BTD submission has been accepted by the FDA, the Company plans to compile a BTD submission for review by the FDA in 3Q2024 in support of the grant of a BTD approval.

Theralase has commenced receiving clinical data from the CSSs with a significant number of patients, who achieved CR, continuing to experience a duration of their CR beyond 450 days, with some patients demonstrating CR for up to 3 years and counting, post the primary Study Procedure.

Study II Preliminary Clinical Data:

Performance to Primary, Secondary and Tertiary Objectives:

The interim clinical data above demonstrates that:

For the primary objective, 63% of patients provided the Study Procedure (Study Drug activated by the Study Device) demonstrated a Complete Response ("CR") (negative cystoscopy and negative urine cytology, among other definitions). Including patients, who demonstrated an Indeterminate Response ("IR") (negative cystoscopy and positive or suspicious urine cytology), the Total Response ("TR") increases to 71%. This represents almost 3 out of 4 Bacillus Calmette Guérin ("BCG")-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC") Carcinoma In-Situ ("CIS") patients treated with Theralase’s unique Study Procedure are demonstrating complete destruction of their CIS bladder cancer within their bladders.

For the secondary objective, 44% (almost 1 out of 2) patients, who demonstrated a CR at any point in time continued to demonstrate a CR at 15 months from date of first treatment with 46% of patients demonstrating a TR.

> 90% of patients who demonstrated a CR at 450 days continue to demonstrate this response beyond 450 days.

For the tertiary objective, no patients have been diagnosed with a Serious Adverse Event ("SAE") directly related to the Study Drug or Study Device 100% (65/65).

Note:

For patients to be included in the statistical clinical analysis they must be enrolled in Study II, provided the primary Study Procedure and evaluated by a Principal Investigator ("PI") at the 90 days assessment visit (cystoscopy and urine cytology)
One patient passed away prior to their 90 days assessment and is therefore not included in the efficacy statistical analysis, only in the safety statistical analysis; therefore, there are 65 patients that have been statistically analyzed for efficacy.
Evaluable Patients are defined as patients who have been evaluated by a PI and thus excludes a patient’s clinical data at specific assessment days, if that clinical data is pending.
7 patients have been enrolled and provided the primary Study Procedure but, have not been evaluated at their 90 day assessment; therefore, 65 patients are considered Evaluable Patients at 90 days, with 41 patients considered Evaluable Patients at 450 days.
The data analysis presented above, should be read with caution, as the clinical data is interim in its presentation, as Study II is ongoing and new clinical data collected may or may not continue to support the current trends, with clinical data still pending.
Patient Response Chart:

The Swimmer’s plot below is a graphical representation of the interim clinical results (n=41) for patients who achieved a CR at any point in time and their response over 1080 days, graphically demonstrating a patient’s response to a treatment over time. As can be seen in the plot, clinical data is still pending for patients, who have demonstrated an initial CR at 90 days and continue to demonstrate a duration of that response.

The Swimmer’s Plot illustrates:

63% (41/65) Evaluable Patients achieved CR at any point in time, with 44% (18/41) patients, who demonstrated CR, continuing to demonstrate CR at 450 days and thus achieving the primary and secondary objectives of Study II.
41% (17/41) Evaluable Patients demonstrate CR beyond 450 days.
Note: This is interim clinical data and clinical data is still being collected, but all indications demonstrate that the study has achieved its primary, secondary and tertiary objectives.

Kaplan-Meier Curve:

The Kaplan-Meier ("KM") Curve illustrates graphically, for patients who have achieved a CR, the duration of CR and probability of that CR continuing in the future.

Note: The information on the time-to-outcome event is not available for all patients in this analysis, as not all patients have been assessed at all available assessment visits. Only patients that achieved the primary objective (CR at any point in time) have been analyzed and data is plotted relative to the date at which their first CR was observed. The "X" denotes censored observations (subjects who achieved CR at their last assessment visit and are currently on-study or have been removed from study). Thus, the KM Curve estimates the risk of a patient failing to maintain a CR over time, according to currently available interim data.

In summary, the interim clinical data demonstrates that patients consenting to participate in Study II have a 63% chance of achieving CR.

If CR is obtained, then the patient has a 48.3%, 42.3% and 33.8% chance of remaining cancer free for 1, 2 and 3 years, respectively.

Serious Adverse Events

For 72 patients treated in Study II, there have been 14 Serious Adverse Events ("SAEs") reported:

3 – Grade 2 (resolved within 1, 1 and unknown days, respectively)
7 – Grade 3 (resolved within 1, 2, 3, 4, 4, 82 and unknown days, respectively)
3 – Grade 4 (resolved within 3, 6 and 8 days, respectively)
1 – Grade 5
Theralase believes all SAEs reported to date are unrelated to the Study II Drug or Study II Device.

Note: A SAE is defined as any untoward medical occurrence that at any dose: Is serious or life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or results in death.

Dr. Arkady Mandel, M.D., Ph.D., D.Sc., Chief Scientific Officer of Theralase stated, "The interim clinical data of Study II, to date, has proven to be world-class. Study II has demonstrated an ability to destroy urothelial cell carcinoma in a patient’s bladder for a Total Response ("TR") of 71% and a duration of that TR of 46%, at 450 days. The primary benefits of the Theralase technology versus competitive technologies are: a urologist-led treatment, a single out-patient procedure, high efficacy rates (patients achieve a CR in 63% of the cases with a 44% duration of that CR at 450 days), high probability of the ongoing duration of that complete response (34% ≥ 3 years, based on the Kaplan-Meier Curve analysis of the interim clinical data) and high safety profile (no SAEs directly associated with the Study Drug or Study Device); therefore, the Theralase technology presents a safe, effective alternative therapy for patients, who are at high risk of having their bladder removed."

Roger DuMoulin-White, B.E.Sc., P.Eng., Pro.Dir., President and Chief Executive Officer of Theralase stated, "Based on the interim clinical data accumulated to date, Study II has achieved its primary, secondary and tertiary endpoints and requires only a few additional patients enrolled and follow-up on all patients to complete the study. Theralase expects to complete patient follow-up by mid 2026 with review by Health Canada and the FDA on a marketing approval by end of 2026. The Theralase bladder cancer treatment has been proven clinically to be safe and effective in the treatment of BCG-Unresponsive NMIBC CIS, fulfilling an unmet need of the medical community."

About Study II:

Study II utilizes the therapeutic dose of the patented Study II Drug ("RuvidarTM" or "TLD-1433") (0.70 mg/cm2) activated by the proprietary Study II Device (TLC-3200 Medical Laser System or "TLC-3200"). Study II is focused on enrolling and treating approximately 75 to 100 BCG-Unresponsive NMIBC Carcinoma In-Situ ("CIS") patients in up to 15 Clinical Study Sites ("CSS") located in Canada and the United States.

About RuvidarTM:

RuvidarTM is a peer reviewed, patented PDC currently under investigation in Study II.

On August 12, 2024 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, reported that it will discontinue enrollment in the SELECT-AML-1 Phase 2 clinical trial evaluating the triplet regimen of tamibarotene in combination with venetoclax and azacitidine compared to the doublet regimen of venetoclax and azacitidine in newly diagnosed, unfit patients with acute myeloid leukemia (AML) and RARA gene overexpression (Press release, Syros Pharmaceuticals, AUG 12, 2024, View Source [SID1234645738]). This decision is based on the results of a prespecified interim analysis of the trial.

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Data from 51 patients enrolled in SELECT-AML-1 were reviewed on August 9, 2024. This review included a prespecified non-binding futility analysis conducted on the first 40 randomized patients after the fortieth randomized patient received approximately three months of study drug or discontinued treatment. A similar complete response (CR)/complete response with incomplete hematologic recovery (CRi) rate was observed in the triplet arm (n=20; 65%, CI: 40.8-84.6) and the doublet arm (n=20; 70%, CI: 45.7-88.1). As a result, the probability for success of the SELECT-AML-1 study to demonstrate superiority at the final analysis in 80 randomized patients was considered low, and Syros made the decision to discontinue further enrollment. There were no new safety signals associated with the use of tamibarotene in combination with venetoclax and azacitidine. Patients currently enrolled in SELECT-AML-1 will have the opportunity to remain on study at the discretion of study investigators. Syros plans to present data from SELECT-AML-1 at the 12th Annual Meeting of the Society of Hematologic Oncology (SOHO) in September 2024.

"We are disappointed by this unexpected outcome, especially for people living with AML," said David A. Roth, M.D., Chief Medical Officer of Syros. "In our prior Phase 2 clinical trial, the doublet combination of tamibarotene and azacitidine delivered a 61% CR/CRi rate in newly diagnosed AML patients with RARA overexpression. This supports our conviction in pursuing a doublet strategy in higher-risk MDS, where we are comparing tamibarotene and azacitidine to azacitidine alone. We remain steadfast in our commitment to delivering tamibarotene for the treatment of HR-MDS and look forward to sharing pivotal data from SELECT-MDS-1 by mid-fourth quarter."

Syros continues to evaluate tamibarotene, an oral, selective, retinoic acid receptor alpha (RARα) agonist, in combination with azacitidine in the SELECT-MDS-1 Phase 3 clinical trial in newly diagnosed higher-risk myelodysplastic syndrome (MDS) patients with RARA gene overexpression. The SELECT-MDS-1 trial passed a prespecified futility analysis in the first quarter of 2024 and is continuing as planned, with pivotal CR data expected by the middle of the fourth quarter of 2024.

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

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

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

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

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

About the data

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

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

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

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

About Revumenib

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

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

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

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

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

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

Clinical Program Updates and Upcoming Milestones

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PRT2527 – A potent and highly selective CDK9 Inhibitor

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

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

Second Quarter 2024 Financial Results 

Cash, Cash Equivalents, and Marketable securities:

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

Research and Development (R&D) Expenses:

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

General and Administrative (G&A) Expenses:

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

Net Loss:

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

On August 12, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported financial results and operational updates for the quarter ended June 30, 2024 (Press release, ORIC Pharmaceuticals, AUG 12, 2024, View Source [SID1234645734]).

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"We have made strong progress on advancing the pipeline, deepening strategic relationships, and growing the leadership team to add new functional capabilities," said Jacob M. Chacko, M.D., president and chief executive officer. "We are making good progress on the expansion cohorts for ORIC-114 in three different selected patient populations in NSCLC and have initiated combination dosing for ORIC-944 in prostate cancer. The clinical trial collaboration and supply agreements with Bayer and Johnson & Johnson are pivotal steps in supporting those combination cohorts. Finally, we bolstered our leadership team to add commercial and medical affairs capabilities in advance of the potential initiation of multiple registrational trials in 2025. We look forward to sharing further clinical updates in 2025."

Second Quarter 2024 and Other Recent Highlights

ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor

Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses.
Announced first patients dosed across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated non-small cell lung cancer (NSCLC), including EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), HER2 exon 20 insertion, and EGFR atypical mutations.
Initiated an extension cohort to evaluate ORIC-114 for the treatment of patients with first-line, treatment-naïve EGFR exon 20 insertion NSCLC.
Expect to report updated Phase 1b data in the first half of 2025.
ORIC-944: a potent and selective allosteric inhibitor of PRC2

Initiated dosing of ORIC-944 in combination with NUBEQA (darolutamide) and in combination with ERLEADA (apalutamide) in the ongoing Phase 1b trial for prostate cancer in first half of 2024.
Entered into clinical trial collaboration and supply agreements with Bayer and Johnson & Johnson to support the ongoing Phase 1b trial of ORIC-944 in combinations with AR inhibitors for the treatment of prostate cancer.
Presented preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting demonstrating superior drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors.
Discovery Pipeline:

Presented at the 2024 AACR (Free AACR Whitepaper) annual meeting the first preclinical data on ORIC-613, a potential first- and best-in-class development candidate selectively inhibiting PLK4.
Corporate Highlights:

Expanded the leadership team with the appointment of industry veteran Keith Lui as Senior Vice President of Commercial and Medical Affairs.
Second Quarter 2024 Financial Results

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments totaled $308.5 million as of June 30, 2024, which the company expects will be sufficient to fund its operating plan into late 2026.
R&D Expenses: Research and development (R&D) expenses were $28.9 million for the three months ended June 30, 2024, compared to $18.8 million for the three months ended June 30, 2023, an increase of $10.2 million. For the six months ended June 30, 2024, R&D expenses were $50.9 million, compared to $38.3 million for the six months ended June 30, 2023, an increase of $12.6 million. The increases were due to a net increase in external expenses related to the advancement of product candidates and discovery programs, as well as higher personnel costs, including additional non-cash stock-based compensation of $0.6 million and $1.2 million for the three and six months ended June 30, 2024, respectively.
G&A Expenses: General and administrative (G&A) expenses were $7.1 million for the three months ended June 30, 2024, compared to $6.2 million for the three months ended June 30, 2023, an increase of $0.9 million. For the six months ended June 30, 2024, G&A expenses were $14.1 million, compared to $12.4 million for the six months ended June 30, 2023, an increase of $1.7 million. The increases were primarily due to higher personnel costs, including additional non-cash stock-based compensation of $0.6 million and $1.3 million for the three and six months ended June 30, 2024, respectively.