On November 7, 2024 Onchilles Pharma, a private biotech company pioneering pan-cancer therapeutics that leverage the ELANE pathway, reported the presentation of new preclinical data from its NEU-002 program at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Onchilles Pharma, NOV 7, 2024, View Source [SID1234647942]). The event is being held virtually and at the George R. Brown Convention Center in Houston, Texas from November 6-10, 2024.

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The ELANE pathway is a novel innate immune mechanism that enables potent and selective immunogenic cell death of cancer cells irrespective of immunotype, genotype, anatomical origin while sparing healthy tissue. Onchilles Pharma has leveraged this pathway to develop N17350 and NEU-002, two leading therapeutic candidates designed for intratumoral and intravenous (IV) administration, respectively. N17350 is on track to start Phase 1 clinical trials in 2025 to validate the ELANE pathway in head & neck, skin, breast, and lung cancers.

At SITC (Free SITC Whitepaper) 2024, Onchilles Pharma presented new preclinical data on NEU-002, which allows targeting the ELANE pathway through systemic delivery. NEU-002 addresses the challenges of systemic delivery by overcoming inhibition from serine protease inhibitors and enhancing substrate specificity, thereby extending its potential to treat a broad range of solid tumor types that are well-suited for systemic administration.

Key Preclinical Data Highlights:

Enhanced Specificity and Activity: NEU-002 retains full enzymatic activity in plasma and shows improved substrate specificity, effectively cleaving CD95, its therapeutic target, while sparing known off-target substrates.
Selective Cancer Cell Killing: The NEU-002 candidates selectively induce immunogenic cell death in primary cancer cells derived from ovarian cancer patients, validating their selective killing properties in primary human tissue.
Durable Responses: In preclinical studies using the CT26 tumor mouse model, NEU-002 treatment generated complete responses with resistance to tumor rechallenge, suggesting the potential for immune memory formation.
"The data presented today mark a significant advancement in the systemic targeting of the ELANE pathway," said Lev Becker, Ph.D., Scientific Founder and Chief Scientific Officer of Onchilles Pharma. "The ability to selectively target cancer cells while inducing a sustained immune response could provide durable clinical benefits across a wide range of tumor types."

Court R. Turner, J.D., Co-Founder & Chief Executive Officer, added, "N17350 and NEU-002 represent a transformative approach in oncology, with the potential to redefine the standard of care. We are excited about advancing N17350 into a Phase 1 trial in 2025, providing the clinical proof-of-concept for targeting the ELANE pathway and delivering innovative cancer treatments to patients."

To download the poster, click here.

About the NEU-002 Program and the ELANE Pathway

Onchilles Pharma’s NEU-002 program stems from groundbreaking research by its scientific founder, Dr. Lev Becker, who identified the ELANE pathway as a novel innate immune mechanism where neutrophil elastase (ELANE) selectively kills cancer cells while sparing healthy cells. Published in Cell in 2021, these findings have laid the foundation for developing NEU-002, which is tailored for systemic IV delivery, and N17350, designed for intratumoral administration. By leveraging the ELANE pathway, these candidates offer a unique approach to treat cancer regardless of genetic background, anatomical origin, or immunotype, positioning them as potential game-changers in cancer therapy.

Looking Ahead: Clinical Validation in 2025

Onchilles Pharma plans to initiate a Phase 1 trial of its lead candidate, N17350, in 2025 to validate the ELANE pathway in humans. This trial will further explore the safety and efficacy of this innovative mechanism, representing a significant step toward realizing the potential of ELANE-based therapies.

On November 7, 2024 Nkarta, Inc. (Nasdaq: NKTX), a clinical-stage biopharmaceutical company developing engineered natural killer (NK) cell therapies, reported financial results for the third quarter ended September 30, 2024 (Press release, Nkarta, NOV 7, 2024, View Source [SID1234647941]).

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"We’re encouraged by the early progress that we’ve made in the clinical investigation of NKX019 for autoimmune disease," said Paul J. Hastings, CEO of Nkarta. "Having dosed a first patient in both Ntrust-1 and the Columbia University Irving Medical Center IST, our learnings can help us optimize the execution of our current and future clinical trials. This includes our Ntrust-2 trial, which is on track to initiate enrollment later this year. Safety and accessibility are paramount in autoimmune disease, and we believe that an off-the-shelf, engineered NK cell therapy has the greatest potential to help patients."

Hastings continued, "We have decided to forgo future development of NKX019 in non-Hodgkin lymphoma. In reviewing the clinical data from the latest cohort of patients with large B-cell lymphoma and the evolving treatment landscape, Nkarta will focus its efforts on autoimmune diseases, where we believe NKX019 has potential to transform patient care."

Clinical development of NKX019 for autoimmune diseases advances

•
Dosing of the first patient in Ntrust-1, a clinical trial of NKX019 for the treatment of lupus nephritis. As previously announced, the first Ntrust-1 patient entered screening in June 2024.

•
Dosing of the first patient in the IST of NKX019 in systemic lupus erythematosus at Columbia University Irving Medical Center (CUIMC). As previously announced, the CUIMC IST was initiated in July 2024.
•
Both studies continue to enroll participants.

Anticipated autoimmune milestones 2024-2025

•
Initiation of patient enrollment expected by year-end 2024 in Ntrust-2, a clinical trial of NKX019 for the treatment of systemic sclerosis, myositis and vasculitis. As previously announced, the Investigational New Drug (IND) Application for Ntrust-2 cleared in June 2024.
•
Preliminary clinical data from Ntrust-1 and Ntrust-2 clinical trials planned for 2025.

Update for NKX019 in non-Hodgkin lymphoma (NHL)

•
A cohort of seven patients with heavily pretreated large B-cell lymphoma (LBCL) whose disease progressed following treatment with a CD19 CAR T-cell therapy received NKX019 on Days 0, 3, and 7 following lymphodepletion.
•
There were no cases of Grade >2 cytokine release syndrome (CRS) and no cases of immune effector cell-associated neurotoxicity (ICANS).
•
Five patients achieved a partial response after a first cycle of treatment. One of these five patients achieved a complete response with >6 months durability after receiving a second cycle of treatment.
•
Nkarta aims to report final data from the LBCL cohort at a future medical conference.
•
Nkarta will forgo further development in NHL and prioritize development efforts on autoimmune diseases.

Third Quarter 2024 and Recent Financial Highlights

•
Nkarta had cash, cash equivalents, restricted cash, and investments in marketable securities of $405.3 million as of September 30, 2024.
•
Research and development (R&D) expenses were $25.3 million for the third quarter of 2024. Non-cash stock-based compensation expense included in R&D expense was $1.8 million for the third quarter of 2024.
•
General and administrative (G&A) expenses were $8.5 million for the third quarter of 2024. Non-cash stock-based compensation expense included in G&A expense was $2.3 million for the third quarter of 2024.
•
Net loss was $28.3 million, or $0.39 per basic and diluted share, for the third quarter of 2024. This net loss includes non-cash charges of $5.8 million that consisted primarily of share-based compensation and depreciation expenses.

Financial Guidance

•
Nkarta expects its current cash and cash equivalents will be sufficient to fund its current operating plan into late 2027.

About NKX019

NKX019 is an allogeneic, cryopreserved, off-the-shelf immunotherapy candidate that uses natural killer (NK) cells derived from the peripheral blood of healthy adult donors. It is engineered with a humanized CD19-directed CAR for enhanced cell targeting and a proprietary, membrane-bound form of interleukin-15 (IL-15) for greater persistence and activity without exogenous cytokine support. CD19 is a biomarker for normal B cells as well as those implicated in autoimmune disease and B cell-derived malignancies.

About Ntrust Clinical Trials in Autoimmune Disease

Ntrust-1 and Ntrust-2 are multi-center, open label, dose escalation clinical trials that build on academic studies of durable, drug-free remissions in patients with autoimmune disease after CD19-targeted cell therapy. Both trials will assess the safety of NKX019 in people living with autoimmune diseases as well as its ability to enable long-term remissions via a "reset" of the immune system through the elimination of pathogenic B cells. Per the trial protocols, patients receive three-dose cycles of NKX019 at 1 billion or 1.5 billion cells per dose following single-agent lymphodepletion with cyclophosphamide, an agent with an established safety profile across autoimmune diseases. Leveraging the engineering of NKX019, no patients in either trial will receive supplemental cytokines or antibody-based therapeutics. This approach is designed to evaluate the single-agent activity of NKX019 and facilitate a more rapid path to regulatory approval.

In the Ntrust-1 study (NCT06557265), patients with refractory lupus nephritis receive three-dose cycles of NKX019 following lymphodepletion. Patients in Ntrust-1 may also receive additional cycles to restore response.

Once initiated, Ntrust-2 will enroll patients with systemic sclerosis (scleroderma), idiopathic inflammatory myopathy (myositis), and ANCA-associated vasculitis into parallel cohorts, and NKX019 will be dosed on Days 0, 3, and 7, a regimen that may be advantageous across all Nkarta clinical trials. Each trial is designed to initially enroll up to 12 patients.

About the Investigator-Sponsored Clinical Trial of NKX019 for Systemic Lupus Nephritis

The single-center, single-arm, open-label Phase 1 investigator-sponsored clinical trial is designed to enroll up to 6 patients with systemic lupus erythematosus, regardless of renal involvement, and will evaluate safety and clinical outcomes in a potentially different population than Ntrust-1. Translational and biomarker studies, including autoantibodies, cytokine profiles and pharmacokinetics are also planned. Patients receive NKX019 following single-agent lymphodepletion with cyclophosphamide. The clinical trial is being led by Anca D. Askanase, M.D., M.P.H., Director, Lupus Center at Columbia University Irving Medical Center and the Director of Rheumatology Clinical Trials.

On November 7, 2024 Nimbus Therapeutics, LLC ("Nimbus Therapeutics" or "Nimbus"), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, reported the presentation of new clinical and translational data from its ongoing Phase 1/2 trial of NDI-101150, a novel, oral, potent and selective small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, for the treatment of advanced solid tumors (Press release, Nimbus Therapeutics, NOV 7, 2024, View Source [SID1234647940]). Results will be highlighted in two poster presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, taking place November 6-10, 2024 in Houston, Texas.

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The Phase 1/2 multicenter, open-label trial (NCT05128487) is designed to assess NDI-101150 as a monotherapy (50-200 mg QD dose) and in combination with pembrolizumab (200 mg Q3W) in the treatment of adults with advanced solid tumors. The clinical results being presented at the SITC (Free SITC Whitepaper) Annual Meeting include updated safety data from 53 patients in the dose escalation cohorts (n=41 on monotherapy, n=12 on combination therapy) and additional data from 35 patients in the dose expansion cohorts as well as updated efficacy data from 17 response-evaluable patients with renal cell carcinoma (RCC) who received NDI-101150 monotherapy. Results, as of August 12, 2024, showed:

Safety Profile

NDI-101150 was generally well-tolerated with immune-related adverse events supporting the proposed mechanism of action of HPK1 inhibition, which results in immune activation.
Grade ≥3 treatment-related adverse events (TRAEs) occurred in 14% of all patients exposed to NDI-101150 (n=88). The most common TRAEs were nausea, diarrhea, vomiting and fatigue.
Efficacy and Target Engagement

Treatment with NDI-101150 monotherapy resulted in objective responses in 18% (3/17) of response-evaluable RCC patients, including one complete response (CR) and two partial responses (PRs).
A clinical benefit rate (CR + PR + stable disease [SD] ≥6 months) of 29% (5/17) and a disease control rate of 65% (11/17) were observed in response-evaluable RCC patients treated with NDI-101150 monotherapy.
NDI-101150 effectively inhibited its target across multiple dose levels, providing strong pharmacodynamic evidence of the molecule’s activity in patients.
Supporting Mechanistic Evidence

Analysis of tumor biopsies showed a more robust presence of immune cells post-treatment, with increased numbers of tumor-infiltrating lymphocytes and dendritic cells in the tumor microenvironment.
Comprehensive gene expression profiling demonstrated broad activation of immune-related pathways, including enhanced interferon response and T cell activation signals.
"These clinical results of NDI-101150 are highly encouraging, particularly in the context of renal cell carcinoma patients who have experienced disease progression on prior checkpoint inhibitors," said Nathalie Franchimont, M.D., Ph.D., Chief Medical Officer of Nimbus. "The objective responses and disease control rates seen thus far with NDI-101150 in heavily pretreated patients as well as the current safety profile support further evaluation of NDI-101150 in the clinic."

"The clinical and translational data package being presented at SITC (Free SITC Whitepaper) demonstrates both the therapeutic potential of NDI-101150 and the power of our computational drug discovery engine to design highly selective molecules against challenging targets like HPK1," said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. "The monotherapy activity we observed is particularly noteworthy, as many second-generation immunotherapy compounds have struggled to show clinical benefit on their own. Together with its safety profile and the immune activation signals we’ve observed, these data support NDI-101150’s potential as a novel oral non-checkpoint immunotherapy option for patients who need new treatment approaches beyond current checkpoint inhibitors."

The abstracts are available in the Journal for ImmunoTherapy of Cancer (JITC), the official journal of SITC (Free SITC Whitepaper), here and the details of the poster presentations are as follows:

Title: Ongoing Phase 1/2 Trial of the HPK1 Inhibitor NDI-101150 as Monotherapy and in Combination with Pembrolizumab: Clinical Safety Update and Renal Cell Carcinoma (RCC) Efficacy Analysis

Lead Author: David Sommerhalder, M.D., Director of Clinical Research, NEXT Oncology

Date: Saturday, November 9, 2024

Time: 9:00 a.m. – 8:30 p.m. CST

Category: Clinical Trials in Progress

Abstract Number: 682

Link to poster here.

Title: Tumor Immune Microenvironment Characterization from Pre- and Post-Dose Tumors Collected from a Phase 1/2 Study of NDI-101150, a Hematopoietic Progenitor Kinase 1 (HPK1) inhibitor

Lead Author: Scott Daigle, Senior Director, Translational Medicine, Nimbus Therapeutics

Date: Friday, November 8, 2024

Time: 9:00 a.m. – 7:00 p.m. CST

Category: Biomarkers, Immune Monitoring and Novel Technologies

Abstract Number: 83

On November 7, 2024 NextCure, Inc. (Nasdaq: NXTC), a clinical-stage biopharmaceutical company committed to discovering and developing novel, first-in-class, and best-in-class therapies to treat cancer, reported a business update and announced third-quarter 2024 financial results (Press release, NextCure, NOV 7, 2024, View Source [SID1234647939]).

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"The November SITC (Free SITC Whitepaper) presentation of LNCB74 preclinical data will highlight the differentiation of our B7-H4 ADC from other ADC’s that also target B7-H4. We plan to file an IND in the fourth quarter of this year and advance into Phase 1, shortly following receipt of an FDA safe-to-proceed letter," said Michael Richman, NextCure’s president and CEO. "Additionally, while the NC410 combo has shown encouraging Phase 1b clinical activity in both ovarian cancer and CRC patients, we plan to conclude the current trial and seek a partner to advance the program, allowing us to focus our resources on advancing the development of LNCB74."

Business Highlights and Near-Term Milestones

LNCB74 (B7-H4 ADC)

● Leveraging LigaChem Biosciences, Inc. glucuronidase cleavable site-specific linkage as part of a collaboration agreement that includes a 50-50 cost sharing of external development expenses and certain internal cost sharing associated with the development of the antibody- drug conjugate (ADC) program.
● Preclinical data from LNCB74 (B7-H4 ADC) will be presented at the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November.
● Planned submission of an Investigational New Drug (IND) application in the fourth quarter of this year.

NC410 (LAIR-2 fusion)

● Additional colorectal cancer (CRC) patient Phase 1b clinical data along with biomarker data supporting mechanism of action to be presented at SITC (Free SITC Whitepaper) annual meeting in November.
● As of October 14, 2024 (the cut-off date), 11 patients (4 with ovarian cancer and 7 with CRC) remain in the Phase 1b study evaluating NC410 in combination with pembrolizumab and will continue to be monitored while the study concludes.
● As of the cut-off date, the response rate for the ovarian cancer patients that were immune checkpoint inhibitor (ICI) naïve was 25% based on 5 out of 20 patients, which consisted of 2 partial responses (PRs) at 200 mg, and 3 PRs at 100mg in ICI naïve.
● As of the cut-off date, the 100 mg cohort CRC response rate was 8.3% based on 3 out of 36 patients, which consisted of 3 PRs in ICI naïve, MSS/microsatellite instability-low with a disease control rate (DCR) of 47% (17/36), median disease control (mDC) duration of 8.5 months, and median duration of response of 15.2 months. A 200 mg CRC cohort of 7 showed no clinical responses with a DCR of 86% (6/7) and a mDC duration of 8.3 months.
● Will seek a partner or pursue third party financing to advance NC410 in further clinical trials.

Preclinical Non-Oncology Programs Seeking a Partner or Third Party Financing

● NC181 (ApoE4), a humanized antibody for the treatment of Alzheimer’s disease (AD). In preclinical AD animal models, NC181 has demonstrated amyloid clearance, prevention of amyloid deposition, plaque clearance and reduced neuroinflammation.
● NC605 (Siglec-15), a humanized antibody for the treatment of osteogenesis Imperfecta (OI). Preclinical data reported that NC605 treatment reduced bone loss and enhanced bone quality in mice with OI.
● Both programs could lead to IND filings within 12 to 18 months if financial support from a partner or third parties is secured.

Financial Results for Quarter Ended September 30, 2024

● Cash, cash equivalents, and marketable securities as of September 30, 2024 were $75.3 million as compared to $108.3 million as of December 31, 2023. The decrease of $33.0 million was primarily due to cash used to fund operations. NextCure expects financial resources to fund operating expenses and capital expenditures into the second half of 2026.
● Research and development expenses were $8.8 million for the three months ended September 30, 2024, as compared to $11.0 million for the three months ended September 30, 2023. Net costs on the LNCB74 program were more than offset by lower costs on other programs and preclinical development and lower personnel-related costs.
● General and administrative expenses were $3.7 million for the three months ended September 30, 2024, as compared to $4.6 million for the three months ended September 30, 2023. The decrease of $0.9 million was primarily related to lower payroll, lower stock compensation expense and lower insurance costs.
● Net loss was $11.5 million for the three months ended September 30, 2024, as compared to a net loss of $14.3 million for the three months ended September 30, 2023.

On November 7, 2024 Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in genetic testing and precision medicine, reported financial results for its third quarter ended September 30, 2024 and updated its previously issued financial guidance on business performance for the full-year 2024 (Press release, Myriad Genetics, NOV 7, 2024, View Source [SID1234647938]).

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"During the third quarter of 2024, we grew revenue by 11%, compared to the third quarter of 2023, representing a fifth consecutive quarter of double-digit year-over-year revenue growth and have now delivered 13% revenue growth year-to-date as compared to the same nine-month period in 2023. This builds on the 11% revenue growth we reported for the full year 2023 and reflects the strength of our diversified product offerings, improved commercial execution, and the benefits of the enterprise-wide investments made over the last few years to improve customer service and ease of use," said Paul J. Diaz, President and CEO of Myriad Genetics. "We continue to focus on delivering profitable growth and free cash flow and are pleased with the significant progress we have made across the organization. These efforts, combined with prudent management of our cost structure, contributed to Myriad Genetics generating an improved net loss of $22.1 million and over $14 million in adjusted EBITDA in the third quarter. In October 2024, we hosted an investor event where we provided additional detail on our strategic initiatives, including enhancements to our existing products, and an update on our new product pipeline. These new products, once commercialized, have the potential to address a number of large market opportunities where we believe we will have highly differentiated proprietary solutions, providing us opportunities to accelerate growth going forward. These opportunities build on our mission and vision to reach more patients with life-changing precision medicine. Unfortunately, differentiated solutions often face obstacles to gain broad payor acceptance, as we recently experienced with UNH and its updated medical policy on multi-gene panel pharmacogenetic testing. We are disappointed UNH is restricting access to GeneSight, an important tool for healthcare providers, especially primary care providers, to help patients suffering from depression and anxiety to find the right medication treatment. We look forward to sharing additional clinical evidence for GeneSight with UNH and finding a positive resolution for patients."
Financial and Operational Highlights
•Test volumes of 376,000 in the third quarter of 2024 increased 6% year-over-year.
•The following table summarizes year-over-year testing volume changes in the company’s core product categories:

Three months ended September 30, Nine Months Ended September 30,
(in thousands)
2024 2023
% Change
2024 2023
% Change
Product volumes:
Hereditary cancer
74 71 5 % 219 207 5 %
Tumor profiling
13 13 — % 41 45 (9) %
Prenatal 162 156 3 % 506 469 8 %
Pharmacogenomics
127 116 10 % 380 343 11 %
Total 376 356 6 % 1,146 1,064 8 %

•The following table summarizes year-over-year revenue changes in the company’s core product categories:
Three months ended September 30, Nine Months Ended September 30,
(in millions)
2024 2023
% Change
2024 2023
% Change
Product revenues:
Hereditary cancer
$ 90.5 $ 86.5 5 % $ 270.1 $ 238.9 13 %
Tumor profiling
31.6 30.2 5 % 95.1 103.5 (8) %
Prenatal 43.5 39.5 10 % 132.2 111.3 19 %
Pharmacogenomics
47.7 35.7 34 % 129.6 102.9 26 %
Total $ 213.3 $ 191.9 11 % $ 627.0 $ 556.6 13 %

•Gross margin of 70.2% in the third quarter of 2024 increased 20 basis points year-over-year, reflecting operating leverage and improved average revenue per test. Adjusted gross margin in the third quarter of 2024 was 70.6%, an increase of 20 basis points year-over-year.
•Third quarter 2024 operating expenses were $169.8 million, decreasing 13% over the same period in the prior year due to significant legal costs incurred in the third quarter of 2023 that did not repeat in the third quarter of 2024. Operating expenses accounted for 80% of total revenue in the third quarter of 2024, down from 101% of total revenue in the third quarter of 2023. Adjusted operating expenses were $141.0 million, increasing 3% over the same period in the prior year and reflect ongoing investments in technology, research and development offset by cost management activities. Adjusted operating expenses accounted for 66% of total revenue in the third quarter of 2024, down from 72% of total revenue in the third quarter of 2023.
•Operating loss in the third quarter of 2024 was $20.0 million, improving $40.1 million year-over-year; adjusted operating income in the third quarter of 2024 was $9.5 million, improving $11.7 million year-over-year.

Business Performance and Highlights

Oncology
The Oncology business delivered revenue of $82.9 million in the third quarter of 2024.
•Third quarter 2024 hereditary cancer testing revenue in Oncology grew 11% year-over-year, reflecting both volume growth year-over-year and ongoing initiatives to improve average revenue per test.
•Third quarter 2024 tumor profiling revenue of $31.6 million grew 5% year-over-year, as contributions from Precise Tumor and Prolaris were partly offset by a challenged biopharma environment and the sale of the EndoPredict business on August 1, 2024.
•In October 2024, Myriad Genetics entered a collaboration with Flatiron Health, a leading health technology company, that allows physicians to order Myriad Genetics’ MyRisk Hereditary Cancer Test and view the results of the test directly in Flatiron’s cloud-based Electronic Medical Record (EMR) platform, OncoEMR.
•In October 2024, Myriad Genetics received a third patent relating to proprietary methods that generate ultra-sensitive detection of tumor-specific mutations in circulating tumor DNA (ctDNA), which is complementary to two patents granted earlier in the year for the company’s methods of preparing cell-free DNA. These patents support advancing commercialization of the company’s high sensitivity tumor informed molecular residual disease (MRD) assay.
•Myriad Genetics has established a number of additional research collaborations regarding the use of the company’s Precise MRD test for breast cancer patients, with leading cancer research institutions, including The University of Texas MD Anderson Cancer Center and the National Cancer Center Hospital East in Japan. Myriad Genetics has previously announced other MRD collaborations, including a metastatic breast cancer study with researchers at Memorial Sloan Kettering Cancer Center and a prospective pan-cancer study, including breast cancer, led by researchers at the National Cancer Center Hospital East in Japan.

Women’s Health
The Women’s Health business delivered revenue of $82.7 million in the third quarter of 2024.
•Prenatal testing revenue in the third quarter of 2024 grew 10% year-over-year, reflecting volume growth and ongoing initiatives to improve average revenue per test.
•Third quarter 2024 hereditary cancer testing revenue in Women’s Health declined 2% year-over-year with modest volume growth which was offset by the fact that a favorable change in estimate for average revenue per test in the third quarter of 2023 did not repeat in the third quarter of 2024. Year-to-date 2024 hereditary cancer testing revenue in Women’s Health grew 12% compared to the same nine-month period in 2023 as we believe more practitioners have seen the benefit of incorporating MyRisk with RiskScore as part of a comprehensive breast cancer risk assessment program.
•In October 2024, Myriad Genetics initiated a satellite media tour to coincide with new FDA guidelines to drive increased awareness and engagement around the connection between breast density and cancer risk. New FDA guidelines provide that mammography facilities are required to provide all patients receiving a mammogram with a breast density notification.
•In October 2024, Myriad Genetics established a strategic partnership with jscreen, a national organization providing access to genetic testing with a focus on high-risk populations. The partnership intends to reach hundreds of thousands of high-risk adults across the United States through targeted outreach and in-person genetic screenings.

Pharmacogenomics
In the pharmacogenomics business, GeneSight test revenue was $47.7 million in the third quarter of 2024.
•Third quarter 2024 GeneSight testing revenue grew 34% year-over-year, reflecting double-digit test volume growth year-over-year and ongoing initiatives to improve payor coverage and average revenue per test.
•Currently, biomarker legislation for state-regulated plans has passed in 15 states. In many of these states, commercial and managed Medicaid payers have modified their coverage policies to include GeneSight. Additionally, there are a number of states where legislation is in process. Myriad Genetics continues to see an increasing number of payors incorporating, or planning to incorporate, GeneSight into their coverage.
•During the third quarter of 2024, Myriad Genetics expanded payor coverage for several products, including GeneSight. Third quarter saw an additional 17 new contracts and expanded medical policies and coverage, enhancing access to our products, including GeneSight.

•On November 1, 2024, UNH updated its medical policy for pharmacogenetic testing to no longer provide coverage for certain multi-gene panel pharmacogenetic tests, including our GeneSight test, under its commercial and individual exchange benefit plans, effective January 1, 2025. After initial review of the updated policy, the company strongly disagrees with UNH’s decision and its rationale that there is insufficient evidence of efficacy to support coverage of GeneSight. Myriad Genetics is actively engaging with UnitedHealthcare to discuss additional evidence for Myriad Genetics’ proprietary and clinically differentiated mental health medication test, and is seeking to ensure that enrollees continue to have access to the test. We do not believe that the updated policy affects coverage of GeneSight by UNH under Medicare Advantage and managed Medicaid plans or coverage by other payors.

Cash Flow and Liquidity
For the third quarter of 2024, restricted and unrestricted cash increased by $8.6 million. As of the end of the third quarter of 2024, the company had cash and cash equivalents, excluding restricted cash, of $99.9 million and the ability to access an incremental $48.8 million of availability under its asset-based credit facility (the "ABL Facility"). The company had combined liquidity from its unrestricted cash and cash equivalents of $148.7 million.

Financial Guidance
Myriad Genetics does not provide forward-looking guidance on a GAAP basis for the measures on which it provides forward-looking non-GAAP guidance as the company is unable to provide a quantitative reconciliation of forward-looking non-GAAP measures to the most directly comparable forward-looking GAAP measure, without unreasonable effort, because of the inherent difficulty in accurately forecasting the occurrence and financial impact of the various adjusting items necessary for such reconciliations that have not yet occurred, are dependent on various factors, are out of the company’s control, or cannot be reasonably predicted. Such adjustments include, but are not limited to, real estate optimization and transformation initiatives, certain litigation charges and loss contingencies, costs related to acquisitions/divestitures and the related amortization, impairment and related charges, and other adjustments. For example, stock-based compensation may fluctuate based on the timing of employee stock transactions and unpredictable fluctuations in the company’s stock price. Any associated estimate of these items and its impact on GAAP performance could vary materially.