On February 20, 2025 GRAIL, Inc. (Nasdaq: GRAL), a healthcare company whose mission is to detect cancer early when it can be cured, reported business and financial results for the fourth quarter and full year 2024 and provided business updates (Press release, Grail, FEB 20, 2025, View Source [SID1234650428]).

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Fourth quarter revenue grew 26% year-over-year to $38.3 million, and Galleri revenue grew 39% year over year to $31.6 million. Net loss for the quarter was $97.1 million, which includes amortization of Illumina acquisition-related intangible items of $34.6 million. Gross loss was $16.0 million. Non-GAAP adjusted gross profit was $17.9 million and non-GAAP adjusted EBITDA was $(84.0) million.1

For the full year, total revenue grew 35% year over year to $125.6 million, and Galleri revenue grew 45% year over year to $108.6 million. Net loss for the year was $2.0 billion, which includes goodwill and intangible assets impairment of $1.4 billion and amortization of Illumina acquisition-related intangible items of $138.3 million. Gross loss was $78.0 million. Non-GAAP adjusted gross profit was $57.8 million and non-GAAP adjusted EBITDA was $(483.5) million.1

Additionally, TRICARE Health Insurance recently added GRAIL’s Galleri multi-cancer early detection test as a covered benefit. The Galleri test will be covered for patients who are 50 years or older with an elevated risk for cancer. TRICARE is one of the largest health plans in the U.S. and serves active duty service members, National Guard and Reserve members, retirees and their families.

"2024 was a transformational year for GRAIL as we completed the separation from Illumina in June 2024, and completed study visits for our two registrational studies in July," said Bob Ragusa, Chief Executive Officer at GRAIL. "We executed a restructuring in the third and fourth quarters, and continue to focus on business efficiencies while also growing commercially. We plan to read out our registrational studies in 2025 and 2026 and complete our modular PMA submission in the first half of 2026."

For the three months ended December 31, 2024, as compared to the three months ended December 31, 2023, GRAIL reported:

Revenue: Total revenue, comprised of screening and development services revenue, was $38.3 million, an increase of $7.9 million or 26%.
Net loss: Net loss was $97.1 million, an improvement of $90.5 million or 48%.
Gross loss: Gross loss was $16.0 million , an improvement of $2.7 million or 14%.
Adjusted gross profit1: Adjusted gross profit was $17.9 million, an increase of $2.6 million or 17%.
Adjusted EBITDA1: Adjusted EBITDA was $(84.0) million, an improvement of $39.4 million or 32%.
For the twelve months ended December 31, 2024, as compared to the twelve months ended December 31, 2023, GRAIL reported:

Revenue: Total revenue, comprised of screening and development services revenue, was $125.6 million, an increase of $32.5 million or 35%.
Net loss: Net loss was $2.0 billion, an increase of $561.3 million or 38%, primarily driven by goodwill and intangible asset impairment.
Gross loss: Gross loss was $78.0 million, an improvement of $17.6 million or 18%.
Adjusted gross profit1: Adjusted gross profit was $57.8 million, an increase of $17.6 million or 44%.
Adjusted EBITDA1: Adjusted EBITDA was $(483.5) million, an improvement of $40.3 million or 8%.
Cash position: Cash, cash equivalents, restricted cash and short-term marketable securities totaled $766.8 million as of December 31, 2024.

Additional business highlights include:

Patient Reported Outcomes for GRAIL’s Galleri Multi-Cancer Early Detection Blood Test Published in Lancet Oncology. Analysis of patient reported outcomes from PATHFINDER indicate minimal patient distress associated with multi-cancer early detection (MCED) testing, and high overall satisfaction with the MCED test was reported across participant groups regardless of signal detection status and eventual diagnosis. Most participants reported they were "likely"/"very likely" to adhere to future guideline recommended screening tests as recommended by their healthcare provider.

GRAIL and Quest Diagnostics Announced Availability of GRAIL’s Galleri MCED Test Through the Quest Diagnostics Test Ordering System. The Quest Diagnostics connectivity system enables providers in the United States to order and receive reports of laboratory tests electronically through Quest’s Quantum laboratory portal and more than 900 electronic health record systems. More than 500,000 providers used the Quest connectivity system last year. The integration will help streamline the process of ordering the Galleri test and increase availability by allowing patients access to the test at any of the approximately 7,400 patient access points nationwide. Patients can now go directly to Quest without needing to bring a Galleri test kit to the blood draw appointment.

Conference Call and Webcast

A webcast and conference call will be held today, February 20, 2025, at 1:30 p.m. PT / 4:30 p.m. ET. Individuals interested in listening to the conference call may access it on the investor relations section of GRAIL’s website at investors.grail.com.

A replay of the webcast will be available on GRAIL’s website for 30 days.

On February 20, 2025 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the Company will participate in TD Cowen’s 45th Annual Health Care Conference. Company management will participate in a fireside chat on Wednesday, March 5, 2025, at 7:30 a.m. PT / 10:30 a.m. ET / 3:30 p.m. GMT (Press release, Jazz Pharmaceuticals, FEB 20, 2025, View Source [SID1234650427]).

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An audio webcast of the fireside chat will be available via the Investors section of the Jazz Pharmaceuticals website at View Source A replay of the webcasts will be archived on the website for 30 days.

On February 20, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported the company has successfully enrolled the first patient in its multicenter, randomized, double-blind Phase III clinical trial of ivonescimab in combination with chemotherapy for first-line treatment for unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) (HARMONi-BC1/AK112-308) (Press release, Akeso Biopharma, FEB 20, 2025, View Source [SID1234650426]). Ivonescimab is a first-in-class PD-1/VEGF bispecific antibody independently developed by the company.

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HARMONi-BC1/AK112-308 study is led by Professor Xu Binghe, a renowned breast cancer expert and academician of the Chinese Academy of Engineering, from the Cancer Hospital of the Chinese Academy of Medical Sciences. Preliminary efficacy data presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting demonstrated that ivonescimab combined with chemotherapy showed significant therapeutic efficacy and also exhibited a favorable safety profile, underscoring its clinical potential for the treatment of locally advanced or metastatic TNBC.

Akeso has strategically positioned ivonescimab within a comprehensive development plan, aiming to reshape the landscape of cancer immunotherapy and establish a new global standard of care. Ivonescimab, in combination with chemotherapy, has been approved in China for the treatment of EGFR-TKI-resistant, non-squamous NSCLC. The New Drug Application (sNDA) for ivonescimab monotherapy as a first-line treatment for PD-L1-positive NSCLC (in comparison to pembrolizumab) is currently under review and has been granted priority status in China.

Three international multicenter Phase III clinical trials, led by our partner Summit Therapeutics, are progressing efficiently or are being initiated:

The HARMONi study, an international multicenter Phase III clinical trial evaluating ivonescimab in combination with chemotherapy for non-squamous NSCLC with progression after third-generation EGFR-TKI treatment, has had patient enrollment completed and has received Fast Track Designation (FTD) from the U.S. Food and Drug Administration (FDA),
The HARMONi-3 study, an international multicenter Phase III clinical trial comparing ivonescimab combined with chemotherapy as first-line treatment for both squamous and non-squamous NSCLC (versus pembrolizumab combined with chemotherapy),
The HARMONi-7 study, an international multicenter Phase III clinical trial evaluating ivonescimab monotherapy as first-line treatment for PD-L1 high-expressing NSCLC (versus pembrolizumab).
Several Phase III clinical trials are progressing efficiently or are being initiated in China, including:

Ivonescimab combined with chemotherapy as first-line treatment for squamous NSCLC (vs. tislelizumab combined with chemotherapy, HARMONi-6/AK112-306),
Ivonescimab combined with chemotherapy as first-line treatment for biliary tract cancer (vs. durvalumab combined with chemotherapy, HARMONi-GI1/AK112-309),
Ivonescimab combined with AK117 (CD47) as first-line treatment for PD-L1 positive head and neck squamous cell carcinoma (vs. pembrolizumab, SOLO-10/AK117-302),
First-line treatment for pancreatic cancer (HARMONi-GI2/AK112-310),
First-line treatment for triple-negative breast cancer (HARMONi-BC1/AK112-308).

On February 20, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing the tuspetinib (TUS)-based triple drug frontline therapy to treat patients with newly diagnosed AML, reported that the Cohort Safety Review Committee (CSRC) monitoring Aptose’s Phase 1/2 TUSCANY trial of tuspetinib in combination with standard of care dosing of venetoclax and azacitidine (TUS+VEN+AZA triplet) has unanimously approved escalating from 40 mg TUS to 80 mg TUS based on its favorable review of data from the first four patients in the trial (Press release, Aptose Biosciences, FEB 20, 2025, View Source [SID1234650425]). The TUS+VEN+AZA triplet is being developed as a frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy.

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No significant safety concerns or dose limiting toxicities (DLTs) have been reported, including no prolonged myelosuppression of subjects in remission. All four subjects treated in the 40 mg cohort remain on study while enrollment is open for the 80 mg cohort.

"With a high level of enthusiasm, our CSRC – comprised of study investigators that include key leaders in the development of therapeutic agents for AML – recommended we escalate dosing in our TUSCANY trial with tuspetinib," said Rafael Bejar, M.D., Ph.D., Chief Medical Officer of Aptose. "The lack of prolonged myelosuppression with no DLT’s and several complete responses, including an MRD-negative CRh noted early in treatment, is truly encouraging. As one our chief investigators remarked, if the TUS+VEN+AZA triplet shows efficacy and tolerability in difficult-to-treat AML populations with little myelosuppression, tuspetinib could be a game changer for frontline AML treatment."

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study

Tuspetinib based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 trial with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Responses to TUS were also observed in those with prior-VEN and prior-FLT3 inhibitor (FLT3i) therapies, those with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.

The TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS will be administered in 28-day cycles, beginning at 40 mg once daily, with dose escalations planned after a safety review of each dose level. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available.

In January 2025, Aptose announced the initiation of the TUSCANY trial and dosing in the first cohort of newly diagnosed AML patients with the lowest starting dose (40 mg) of TUS as part of the TUS+VEN+AZA triplet, and the early data reveal promising clinical safety and antileukemic activity:

To date, four newly diagnosed AML patients have received the lowest dose of TUS (40 mg) as part of the (TUS+VEN+AZA) combination.

Three patients with unmutated (wildtype) FLT3 (FLT3-WT) completed Cycle 1 of treatment with no dose-limiting toxicities (DLTs) and no TUS dose adjustments.

Two FLT3-WT patients achieved complete remissions (CR and CRh) by the end of Cycle 1.
Notably, a patient with biallelic TP53 mutations and a complex karyotype obtained CR.

The third FLT3-WT patient experienced significant reductions in bone marrow leukemic blasts during Cycle 1 and remains on therapy in Cycle 2.

The fourth patient, harboring FLT3-ITD and NPM1 mutations, is currently dosing in Cycle 1 and is not yet eligible for response evaluation.

Pharmacokinetic (PK) analyses for TUS show plasma levels unaffected by the addition of AZA, providing predictability and avoiding the need for dose alterations due to PK interactions.
Similarly, VEN plasma levels in Cycle 1 are consistent with published results and the prior TUS/VEN APTIVATE study in R/R AML, indicating no clinically significant interactions with TUS.

More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov.

On February 20, 2025 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, reported multiple oral and poster presentations, including an oral presentation of additional analyses from the ongoing Phase 2 RAMP 201 (ENGOT-ov60/GOG-3052) trial evaluating the investigational combination of avutometinib plus defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC), at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women’s Cancer, to be held on March 14-17 in Seattle, Washington (Press release, Verastem, FEB 20, 2025, View Source [SID1234650424]). Verastem will also have an exhibition booth (#622) at the meeting where it will be available to discuss its ongoing cancer research.

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"The presentation of the RAMP 201 primary analysis, which served as the basis of the acceptance of our NDA that is under Priority Review with the FDA, includes additional subgroup analysis by KRAS mutational status," said Dan Paterson, president, and chief executive officer of Verastem Oncology. "We look forward to sharing these learnings with many of the world’s leading gynecologic oncologists at SGO as part of our continued commitment to people living with recurrent low-grade serous ovarian cancer. We also recognize the importance of these findings to the broader cancer community as part of our growing pool of data reinforcing the potential to change expectations in managing RAS/MAPK pathway-driven cancers."

Oral Presentation:

Abstract Title: Avutometinib + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer (ENGOT-ov60/GOG-3052/RAMP 201): Dose Intensity and Subgroup Analysis
Presenter: Rachel Grisham, M.D.
Session: Focused Forum XV: Ongoing IMPACT
Date/Time: Monday, March 17, 2025, 9:15 am PST
Oral Presentation​ – Investigator-Sponsored Trial:

Abstract Title: A Phase II Study of Avutometinib and Defactinib in Advanced or Recurrent Gynecologic Mesonephric Cancer: Interim Results
Presenter: Rachel Grisham, M.D.
Session: Focused Forum IV: Finding IMPACT: The Needle in the Haystack​
Date and Time: Saturday, March 15, 2025, 4:15 pm PST
Preclinical Virtual Poster​:

Abstract Title: Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK clamp Avutometinib and FAK Inhibitor in Low-Grade Serous Ovarian Cancer with Acquired Resistance to Chemotherapy and Aromatase Inhibitor
Study Author: Cem Demirkiran, M.D.
About the Avutometinib and Defactinib ​​Combination

Avutometinib is an oral RAF/MEK clamp that potently inhibits MEK1/2 kinase activities and induces inactive complexes of MEK with ARAF, BRAF, and CRAF, potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of the MEK-only inhibitors.

Defactinib is an oral, selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2), the two members of the focal adhesion kinase family of non-receptor protein tyrosine kinases. FAK and Pyk2 integrate signals from integrin and growth factor receptors to regulate cell proliferation, survival, migration, and invasion. FAK activation has been shown to mediate resistance to multiple anti-cancer agents, including RAF and MEK inhibitors.

Verastem Oncology is currently conducting clinical trials with avutometinib with and without defactinib in RAS/MAPK-driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (GOG-3097/ENGOT-ov81/NCRI) (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC).

Verastem was granted Priority Review and a Prescription Drug User Fee Act (PDUFA) date of June 30, 2025, for its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA), for the investigational combination of avutometinib and defactinib in adults with recurrent KRAS mutant LGSOC who received at least one prior systemic therapy. Verastem initiated a rolling NDA in May 2024 to the FDA and completed its NDA submission in October 2024. The FDA granted Breakthrough Therapy Designation for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy, in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology has established a clinical collaboration with Amgen to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib in both treatment-naïve patients and in patients whose KRAS G12C mutant non-small cell lung cancer progressed on a G12C inhibitor as part of the RAMP 203 trial (NCT05074810). Verastem has received Fast Track Designation from the FDA for the triplet combination in April 2024. RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award. FDA granted Orphan Drug Designation to the avutometinib and defactinib combination for the treatment of pancreatic cancer.