On November 20, 2024 The Leukemia & Lymphoma Society (LLS) reported the company will present new data from its Beat AML Master Clinical Trial and Pediatric Acute Leukemia (PedAL) Master Clinical Trial at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, The Leukemia & Lymphoma Society, NOV 20, 2024, View Source;lymphoma-society-lls-data-at-ash-provides-glimpse-into-the-future-of-blood-cancer-treatment-302310609.html [SID1234648529]).

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The findings from LLS’s convened master clinical trials show great progress and are helping shape the treatment landscape for acute leukemias. Updated results show that more than half of a group of children with relapsed acute leukemias achieved remission after receiving a combination of treatments. Additional data indicate that IDH inhibitors as single agent or in combination with low-intensity therapies may be a viable treatment option for older adults with acute leukemias.

LLS will also support its more than 150 funded researchers, as well as more than a dozen current and former LLS Therapy Acceleration Program (TAP) biotech company partners, who will present the latest updates from their ongoing clinical trials.

"For 75 years, LLS has funded physician-scientists and researchers who take risks, think big and test bold ideas," says Lee Greenberger, Ph.D., LLS’s Chief Scientific Officer. "Our strategic investments have helped advance more than 70% of blood cancer treatments approved by the FDA over the past 20 years and I am encouraged to see how the latest data at ASH (Free ASH Whitepaper) will lead to remarkable advances for patients."

Health equity is also a major focus of findings from several investigators funded through the LLS Equity in Access and IMPACT grant programs, which:

Show that there’s significant underrepresentation of women and racial and ethnic minorities in clinical trial enrollment
Provide patient recommendations on how to address disparities in people living with multiple myeloma
Share insights on how to address barriers to opening clinical trials in a community-oncology setting
Demonstrate the disparities in access to care and services depending on the type of insurance coverage.
"LLS has an incredible track record of success across its research, health equity, patient advocacy, and education and support services," says E. Anders Kolb, M.D., The Leukemia & Lymphoma Society’s President and CEO. "The breadth of research we support every year at ASH (Free ASH Whitepaper) reinforces our commitment to improve and extend the lives of blood cancer patients and accelerate progress."

Gwen Nichols, M.D., LLS’s Chief Medical Officer, will join a panel at the Annual ASH (Free ASH Whitepaper) Clinicians in Practice luncheon on December 8, 2024, focused on the future of artificial intelligence in blood cancer.

Drs. Kolb, Nichols and Greenberger are available to provide perspectives on pivotal data presented at ASH (Free ASH Whitepaper), including the promise of menin inhibitors to change the leukemia treatment landscape.

Following is an overview of compelling data from LLS that will be presented at ASH (Free ASH Whitepaper):

Reshaping How Adults with Acute Myeloid Leukemia are Treated

Nearly 1,600 patients with AML have received genomic screening within seven days of diagnosis and more than 500 have enrolled in one of the many Beat AML precision treatment subtrials, which so far have targeted 15 distinct types of AML.

Patients enrolled in Beat AML have achieved improved survival and better quality of life compared to patients receiving standard-of-care chemotherapy.

Beat AML also recently opened its first clinical subtrial to investigate the safety and efficacy of lomonitinib (ZE46-0134) in patients with FLT3-mutated relapsed or refractory AML in partnership with Eilean Therapeutics.

These new findings from Beat AML subtrials will be presented at ASH (Free ASH Whitepaper):

Title & Poster Number

Date/Time

Location

Poster 1564 – Demographics, Characteristics, Survival and Outcomes in Older, Untreated, Acute Myeloid Leukemia Patients with NPM1 Mutations or KMT2A rearrangements from the Beat AML Master Clinical Trial

Saturday, Dec. 7, 2024

5:30-7:30 PM

San Diego Convention Center

Halls G-H

Poster 4324 – Outcomes and Survival in Newly Diagnosed, Older, Acute Myeloid Leukemia Patients from the Beat AML Master Trial in the Venetoclax/Azacitidine Age

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4325 – IDH2 Mutation Is Associated with Favorable Outcome Among Older Adults with Newly Diagnosed Acute Myeloid Leukemia Treated with Lower-Intensity Therapy

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

LLS Executive Research Strategy Lead Ashley Yocum, Ph.D., is available to discuss Beat AML findings.

Revolutionizing the Treatment and Care of Children with Blood Cancer

LLS’s PedAL is fundamentally revolutionizing how children with pediatric leukemia are being treated while building a foundation that addresses major roadblocks to care.

LLS will present updated findings from the PedAL Screening Trial (APAL2020SC), which is actively enrolling in the U.S., Canada, Australia, and New Zealand. This LLS-convened and led screening trial assesses individual clinical and biological characteristics that can inform a family’s choice of standard treatment or enrolling in a clinical trial.

In addition to the PedAL Screening Trial, a treatment trial is open across 74 international sites. LLS anticipates the opening of a second PedAL global treatment trial soon.

Title & Poster Number

Date/Time

Location

Poster 4233 – Molecular Features, Treatments and Outcomes for Pediatric AML Patients from APAL2020SC Pediatric Acute Leukemia (PedAL) Screening Trial

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Chief Medical Officer Gwen Nichols, M.D., is available to provide updates on LLS PedAL and provide perspective on important clinical data coming out of ASH (Free ASH Whitepaper).

Driving the Latest Blood Cancer Developments Through Research Funding

Blood cancer physician-scientists and researchers are transforming the way we treat this disease, but they cannot do this groundbreaking work alone. LLS is helping to lead this charge by funding some of the most innovative research projects around the world focused on bringing blood cancer patients much needed new treatments.

LLS currently provides more than $300 million in academic biomedical research grants to investigators across 16 countries and 30 U.S. states to accelerate how we treat all blood cancers. LLS recently announced its latest round of multi-year grants, which includes research into the development of leukemia in children with Down syndrome.

Here are some of the latest research advances across a variety of blood cancers that several LLS grantees will present at ASH (Free ASH Whitepaper):

Title & Poster Number

Date/Time

Location

Oral 969 – Venetoclax Plus Azacitidine for Newly Diagnosed Younger Acute Myeloid Leukemia Patients Independent of Fitness for Intensive Chemotherapy

Monday, Dec. 9, 2024

5:00 PM

Manchester Grand Hyatt San Diego, Grand Hall B

Oral 321 – Machine Learning Derived Three-Parameter Prognostic Model for Survival in Patients with BPDCN

Saturday, Dec. 7, 2024

4:30 PM

Manchester Grand Hyatt San Diego, Seaport Ballroom EFGH

Oral 1011 – Combined Pirtobrutinib, Venetoclax, and Obinutuzumab As First-Line Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)

Monday, Dec. 9, 2024

5:00 PM

Marriott Marquis San Diego Marina, Grand Ballroom 8-9

Oral 739 – Follicular Dendritic Cells Represent a Therapeutic Vulnerability in Early Follicular Lymphoma

Monday, Dec. 9, 2024

10:30 AM

Marriott Marquis San Diego Marina, Grand Ballroom 5-6

Oral 102 – Acute GvHD of the Gut Is Associated with Minor Histocompatibility Antigens Cross-Reactive Against Gut-Tropic Viral Epitopes

Saturday, Dec. 7, 2024

10:45 AM

San Diego Convention Center Ballroom 20CD

Oral 671 – A High-Fiber Dietary Intervention (NUTRIVENTION) in Precursor Plasma Cell Disorders Improves Biomarkers of Disease and May Delay Progression to Myeloma

Sunday, Dec. 8, 2024

5:30 PM

Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26

Oral 755 – JAK2V617F Mutant MPN Cells Support Parallel Evolution of Independent Leukemic Clones

Monday, Dec. 9, 2024

11:30 AM

Manchester Grand Hyatt San Diego, Grand Hall C

Oral 857 – A Multiomic Analysis of Waldenstrom’s Macroglobulinemia Identifies Three Subtypes of Disease Based on Impaired Plasma Cell Differentiation

Monday, Dec. 9, 2024

3:45 PM

Marriott Marquis San Diego Marina, Pacific Ballroom Salons 18-19

Poster 3127 – Favorable Safety Profile and Durable Responses to Pmb-CT01 (BAFFR-CAR T Cell) Therapy in Patients with B-Cell Lymphomas Ineligible for or Who Failed CD19-Targeted Therapy, Including CD19-Negative Disease

Sunday, Dec. 8, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Addressing Healthcare Disparities Means a Better Future for Everyone with Blood Cancer

LLS believes every blood cancer patient and survivor should be able to access the care they need when they need it. LLS is addressing healthcare disparities to ensure everyone has a better future through three signature programs:

The Equity in Access Research Program, which provides funding for health services research that seeks to uncover and ultimately address the social, economic, and environmental disadvantages that stand in the way of patients with and survivors of a blood cancer accessing high-quality cancer care and services.
Influential Medicine Providing Access to Clinical Trials (IMPACT) provides funding to major cancer centers around the U.S. to collaborate with community-based hospitals and clinics to bring quality blood cancer clinical trials significantly closer to underrepresented patients.
Underrepresented Minority Medical Student (URM) Research programs, launched in 2023, aim to provide medical students from groups underrepresented in biomedical science the opportunity to participate in blood cancer research and benefit from mentorship that the program also provides. The URM program’s first grantee, Jennifer Lewis, is a co-author on an abstract that has developed a new CAR-T product that shows early promise in treating acute myeloid leukemia.
LLS proudly and gratefully acknowledges the leadership support of Royalty Pharma and the following companies for their support of the Equity in Access Research Program and other initiatives focused on reducing healthcare disparities in blood cancer care and treatment: AstraZeneca Pharmaceuticals LP, Lilly and Bristol Myers Squibb.

Title & Poster Number

Date/Time

Location

IMPACT Grants

Oral 784 – Bringing Hematological Malignancy Clinical Trials to Patients: Mayo Clinic LLS Impact

Monday, Dec. 9, 2024

11:15 AM

Marriott Marquis San Diego Marina, San Diego Ballroom AB

Poster 2322 – Chive-Impact: Establishing the Clonal Hematopoiesis and Inflammation in the Vasculature (CHIVE) Registry and Biorepository in Underserved Areas

Saturday, Dec. 7, 2024

5:30-7:30 PM

San Diego Convention Center

Halls G-H

Equity in Access

Oral 786 – Real-World Analysis of Insurer Rejection Rates for Specialty Oral Anticancer Prescriptions in a Nationwide Sample of Patients with Blood Cancer

Monday, Dec. 9, 2024

11:45 AM

Marriott Marquis San Diego Marina, San Diego Ballroom AB

Oral 792 – Impact of Fee-for-Service Versus Managed Care Medicare Insurance on the Quality of End-of-Life Care Among Older Adults with Blood Cancers

Monday, Dec. 9, 2024

11:45 AM

Manchester Grand Hyatt San Diego, Seaport Ballroom EFGH

Health Services

Poster 5100 – Disparities in phase 2 and 3 clinical trial enrollment for hematologic malignancies

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 5113 – Disparities in clinical trial participation among Medicare beneficiaries with hematologic malignancies from 2006 to 2019: a SEER-Medicare analysis

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Partner Projects

Poster 2383 – A Patient Perspective on Actionable Steps to Address Disparities in Healthcare Among US Patients with Multiple Myeloma

Saturday, Dec. 7, 2024

5:30-7:30 PM

San Diego Convention Center

Halls G-H

URM

Oral 371 – Development of CAR T Cells Targeting U5snRNP200 for the Treatment of Acute Myeloid and B-Lymphoid Leukemias

Saturday, Dec. 7, 2024

5:00 PM

Manchester Grand Hyatt San Diego, Grand Hall C

Senior Vice President of Education Services & Health Research Elisa Weiss, Ph.D., is available to provide perspective on health equity research presented at ASH (Free ASH Whitepaper).

Taking Risks to Accelerate the Development of Innovative Blood Cancer Therapies

LLS TAP provides funding to biotech companies to accelerate the development of innovative blood cancer treatments with the promise of changing the standard of care for blood cancer. As a strategic venture philanthropy program, LLS TAP can invest in research that venture capitalists find too risky.

Since 2017, five LLS TAP-supported therapies have been approved by the FDA or included in the National Comprehensive Cancer Network guidelines. Here are some of the latest research advances across a variety of blood cancers that several LLS TAP company partners will showcase at ASH (Free ASH Whitepaper):

Title & Poster Number

Date/Time

Location

Oral 214 – Ziftomenib Combined with Intensive Induction (7+3) in Newly Diagnosed NPM1-m or KMT2A-r Acute Myeloid Leukemia: Interim Phase 1a Results from KOMET-007

Saturday, Dec. 7

2:45 PM

San Diego Convention Center, Ballroom 20CD

Oral 980 – Results from the First Phase 1 Clinical Study of DR-01, a Non-Fucosylated Anti-CD94 Targeting Antibody in Patients with Relapsed/Refractory Cytotoxic Lymphomas: Dose Escalation and Optimization

Monday, Dec. 9, 2024

4:45 PM

Marriott Marquis San Diego Marina, Pacific Ballroom Salons 15-17

Oral 1008 – IO-202, a Novel Anti-LILRB4 Antibody, with Azacitidine for Hypomethylating Agent-Naive Chronic Myelomonocytic Leukemia: Phase 1b Expansion Cohort Results

Monday, Dec. 9, 2024

5:45 PM

Manchester Grand Hyatt San Diego, Grand Hall D

Poster 2876 – ICT01, an Investigational γ9δ2 T Cell Activator, Added to Azacitidine-Venetoclax Achieves Frequent and Early Complete Remissions in Adults with AML Unfit for Intensive Induction Chemotherapy: Interim Results from the Ongoing Open-Label, Randomized Phase 1 Study Eviction

Sunday, Dec. 8, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 3052 – Investigating the Novel Combination of the Innate Cell Engager (ICE) Acimtamig with Off-the-Shelf Allogeneic Natural Killer Cells AlloNK in Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Initial Results of the Phase 2 Luminice-203 Study

Sunday, Dec. 8, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4265 – Encouraging Efficacy of Bexmarilimab with Azacitidine in Relapsed or Refractory MDS in Bexmab Ph1/2 Study

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4395 – EO2463 Peptide Immunotherapy in Patients with Newly Diagnosed Asymptomatic Follicular Lymphoma Results in Monotherapy Objective Clinical Responses Linked with Anti-Peptide Specific CD8 Memory T Cell Responses: The EONHL1-20/Sidney Study

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

Poster 4433 – Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of KT-333, a Targeted Protein Degrader of STAT3, in Patients with Relapsed or Refractory Lymphomas, Leukemia, and Solid Tumors

Monday, Dec. 9, 2024

6:00-8:00 PM

San Diego Convention Center

Halls G-H

On November 20, 2024 the National Medical Products Administration (NMPA) reported on its official website that the NMPA approved the listing of Zorifertinib Hydrochloride Tablets (trade name: Zorifer), a Class 1 innovative drug, developed by Alpha Biopharma (Press release, Alpha Biopharma, NOV 20, 2024, View Source [SID1234648530]). This product is indicated for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) accompanied with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) substitution mutation and central nervous system (CNS) metastases.

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Zorifertinib is the first drug in the world to launch a registration clinical trial specifically for advanced NSCLC with CNS metastases and achieve remarkable results. It is also the only* EGFR tyrosine kinase inhibitor (EGFR-TKI) currently available that was explicitly designed as non-blood-brain barrier efflux protein substrates and can penetrate the blood-brain barrier 100%.

The EVEREST trial, an international multi-center randomized controlled phase III trial of Zorifertinib, demonstrated its superior ability to control intracranial lesions. The trial enrolled patients with more severe disease, most of whom had EGFR L858R mutations or had more than 3 intracranial lesions. Zorifertinib showed a significant benefit in overall progression-free survival (PFS), with intracranial PFS reaching 17.9 months, and it significantly reduced the risk of intracranial progression/death by 37% (P = 0.0018). Furthermore, Zorifertinib demonstrated consistent and significant benefits in subgroups of patients with intracranial symptoms, EGFR L858R mutations, and more than 3 intracranial lesions.

As the global lead Principal Investigator (PI) for the EVEREST study, Professor Wu Yilong from Guangdong Provincial People’s Hospital mentioned that while several drugs have been approved for EGFR mutated NSCLC, there is still a lack of clinical head-to-head randomized controlled studies specifically targeting drug therapy for lung cancer with CNS metastases. The EVEREST study is the world’s first large-scale registered international multi-center clinical trial for the treatment of lung cancer with CNS metastases, and it has achieved statistically significant positive results. In the study, the therapeutic advantages of Zorifertinib in various subgroups were observed, and it was verified that all people with EGFR mutated NSCLC and brain metastases could benefit from Zorifertinib therapy. Among patients who were treated with third-generation TKI after progression, a trend of benefit in overall survival was also observed, suggesting that the combination or sequential therapy with third-generation TKI is expected to bring a better prognosis.

Zhang Yong, CEO of Alpha Biopharma, stated that the company is dedicated to developing innovative drugs that are urgently needed in clinical practice. We have collaborated with AstraZeneca to develop Zorifertinib, aiming to address the unmet clinical needs of patients with lung cancer and CNS metastases. Zorifertinib has demonstrated its therapeutic value during the clinical stage and has received support from clinical experts and regulatory authorities. It has become the world’s first approved new generation EGFR-TKI specifically targeting lung cancer with CNS metastases. The company anticipates that Zorifertinib will significantly enhance patient care in the future, offering more effective treatments for individuals with lung cancer and brain metastases.

About Lung Cancer and Central Nervous System Metastasis

In China, lung cancer is the most common and deadliest malignant tumor. In 2022, there were about 1.06 million new cases of lung cancer diagnosed, leading to approximately 730,000 deaths, with non-small cell lung cancer (NSCLC) accounting for around 85% of all cases. In the Chinese NSCLC population, about 38.4% of patients have been found to have EGFR mutation-positive, which is identified as one of the driving genes for NSCLC formation.

Central nervous system metastasis is a common occurrence in NSCLC patients, with approximately 25% of EGFR mutation-positive NSCLC patients having CNS metastases at the time of initial diagnosis. Additionally, 20% to 65% of lung cancer patients will develop CNS metastases during the course of their disease. Poor blood-brain barrier permeability of therapeutic drugs is one of the reasons why patients experience CNS progression during treatment.

About Blood-Brain Barrier and Efflux Proteins

The blood-brain barrier is a protective shield that prevents drugs from entering the brain. It is made up of tightly packed brain capillary endothelial cells, surrounded by pericellular, astrocyte terminal, and basement membrane structures. This barrier has high resistance and low permeability, making it challenging for drugs to reach the brain. As a result, the brain can act as a safe haven for tumor cells, contributing to the progression of central nervous system (CNS) diseases.

The blood-brain barrier contains a large number of efflux proteins, such as P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP), which are crucial for drug resistance in the development of brain lesions and the survival of tumor stem cells.

Remarks:

The "only … currently available" in this article is valid as of the deadline of Oct. 10, 2024.

References

Cheng H, Perez-Soler R. Leptomeningeal metastases in non-small-cell lung cancer. Lancet Oncol. 2018 Jan;19(1):e43-e55.
Zhou Q, Yu Y, Xing L, et al. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial. Med. Published online October 3, 2024.
Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. Journal of the National Cancer Center, 2024.
Duma N, Santana-Davila R, Molina JR. Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment. Mayo Clin Proc. 2019, 94(8):1623-1640.
Zhang YL, Yuan JQ, Wang KF, et al. Threapleton D, Yang ZY, Mao C, Tang JL. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016 Nov 29;7(48):78985-78993.
Preusser M, Winkler F, Valiente M, Manegold C, Moyal E, Widhalm G, Tonn JC, Zielinski C. Recent advances in the biology and treatment of brain metastases of non-small cell lung cancer: summary of a multidisciplinary roundtable discussion. ESMO (Free ESMO Whitepaper) Open. 2018 Jan 26;3(1):e000262.
Oncology Physician Branch of Chinese Medical Doctor Association, Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care. Chinese Treatment Guidelines for Brain Metastases from Lung Cancer (2021 Edition). Chinese Journal of Oncology, 2021, 43(03): 269-281.
Shetty V, Babu S. Management of CNS metastases in patients with EGFR mutation-positive NSCLC. Indian J Cancer. 2019 Nov;56(Supplement):S31-S37.

On November 20, 2024 Alloy Therapeutics Inc. ( "Alloy"), a biotechnology ecosystem company dedicated to democratizing access to cutting edge drug discovery technologies reported a strategic collaboration and license agreement with Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK "Takeda") to develop Takeda’s proprietary induced pluripotent stem cell (iPSC) derived CAR-T cell platform (iCAR-T) and iPSC-derived CAR-NK platform (iCAR-NK) (Press release, Alloy Therapeutics, NOV 20, 2024, View Source [SID1234648512]). Alloy will focus on accelerating the development of key therapies to overcome solid and hematological malignancies.

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iCAR-T technology was developed as part of the T-CiRA joint research program between Takeda and the Center for iPS Research and Application (CiRA) at Kyoto University. The core technology to differentiate iPSC into immune cells originates from CiRA’s Shin Kaneko’s laboratory. iCAR-T has potential to develop ‘off-the-shelf’ cell therapies, offering the potential for best-in-class performance with enhanced potency, and significantly lower manufacturing costs compared to autologous cell therapy.

"iCAR-T is one of our flagship projects graduating from T-CiRA, our decade-long joint research program between Takeda and CiRA. This agreement between Takeda and Alloy aims to advance iCAR-T from discovery to clinical development," said Yasushi Kajii, Head of R&D Japan Region at Takeda. "We are impressed with Alloy’s corporate culture of valuing platform technologies, flexibility in collaboration, patient-centric mindset, and company creation abilities, all of which were key elements to our decision to work with Alloy. We look forward to seeing iCAR-T and iCAR-NK blossom as the technology advances to its next phase."

Under the agreement, Alloy gains co-exclusive rights to commercialize iCAR-T and iCAR-NK products for oncology indications. Alloy will leverage synergies across its unique business model to further advance the iCAR-T/NK platform while enabling broader access to the technology for biotech and pharma partners to develop therapies for cancers including solid tumors. Future clinical validation and platform enhancements will further strengthen the platform.

"We are honored and excited to be chosen by Takeda to collaborate in fulfilling the promise of iPSC," said Errik Anderson, Founder, Chairman & CEO of Alloy. "This is another instance of how Alloy’s flexible approach allows us to enable the global scientific community with cutting edge technologies designed for rapid, successful drug development. We believe a robust engagement with the ecosystem will play a critical role in unlocking the vast potential of iPSC and enabling the next generation of cancer therapeutics."

To support these efforts, Alloy is establishing a Japanese subsidiary at Shonan Health Innovation Park in Kanagawa Prefecture, to be led by Victor Stone (Yoshihide Ishii) as the Head of Alloy Cell Therapies and Alloy Therapeutics Japan.

On November 20, 2024 Remix Therapeutics (Remix), a clinical-stage biotechnology company developing small molecule therapies to modulate RNA processing and address the underlying drivers of disease, reported an upcoming oral presentation at the 66th ASH (Free ASH Whitepaper) Annual Meeting taking place from December 7-10, 2024, in San Diego, CA (Press release, Remix Therapeutics, NOV 20, 2024, View Source [SID1234648531]). Results demonstrate oral dosing of REM-422, a selective mRNA degrader of the MYB oncogene, leads to robust anti-leukemic activity observed both as a monotherapy and in combination across a genetically diverse set of preclinical models of acute myeloid leukemia (AML), including eradication of AML blasts in engrafted patient-derived xenograft (PDX) models of AML. The presentation also highlights the differentiated mechanism of action of REM-422 as it can be combined effectively with other agents used in the treatment of AML/MDS and retains activity in cell models engineered with mutations known to confer resistance to other targeted agents.

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"The preclinical data for REM-422 provide strong therapeutic rationale for our ongoing Phase I study in AML and High-Risk MDS," said Peter Smith, Ph.D., President and Chief Executive Officer of Remix Therapeutics. "REM-422 is the first compound from our REMaster platform to enter clinical development. Its unique mechanism of action, coupled with the robust anti-leukemic activity observed both as a monotherapy and in combination, positions REM-422 as a promising candidate to address the unmet needs in these patient populations."

The MYB oncogenic transcription factor plays a crucial role in hematopoietic cell differentiation and proliferation. Its dysregulation and aberrant activity have been identified in various cancers, including adenoid cystic carcinoma (ACC), AML, acute lymphoblastic leukemia (ALL), and lymphoma. In AML, functional genomics studies have demonstrated a lineage-wide dependency on MYB, consistent with its involvement in disease driven by multiple oncogenic abnormalities (e.g. MLLr, NPM1, FLT3, p53, etc.).

REM-422 is a first-in-class, potent, selective, oral small molecule degrader of MYB mRNA currently in clinical development for AML/HR-MDS (NCT06297941) and ACC (NCT06118086). It functions by inducing the inclusion of a normally unused ‘poison exon’ (PE) in the MYB pre-mRNA transcript, activating the nonsense-mediated decay pathway and preventing MYB protein expression.

Details for the oral presentation are as follows:

Title: REM-422, a Small Molecule MYB mRNA Degrader, Demonstrates Anti-Leukemic Activity As Monotherapy and in Combination with Standards of Care in Preclinical Models of AML
Speaker: Samantha Levin-Furtney, Scientist, Remix Therapeutics
Session: 604- Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: New Targets and Drugs
Date: Monday, December 9, 2024
Time: 3:30 PM (Session time: 2:45-4:15 PM)
Location: Manchester Grand Hyatt San Diego, Seaport Ballroom ABCD

About REM-422
REM-422 is a first-in-class, potent, selective, and oral small molecule mRNA degrader that induces the reduction of MYB mRNA and subsequent protein expression. REM-422 functions by facilitating the incorporation of poison exons within the mRNA transcript, leading to nonsense-mediated decay (NMD) of the transcript. REM-422 addresses MYB dysregulation, a driver of oncogenesis, upstream of protein expression.

About AML/HR-MDS
Acute myeloid leukemia (AML), a rare cancer of the blood and bone marrow, is the most common type of acute leukemia in adults. AML is caused by genetic mutations within bone marrow cells, which in turn causes the production of leukemic white blood cells that crowd out healthy blood cells. This may cause problems with bleeding, infection, and anemia. Myelodysplastic Syndromes (MDS) are disorders of blood-forming units in the bone marrow. High-risk (HR)-MDS patients have a higher percentage of blast cells in the bone marrow and that, in many cases, progresses to AML. There are several approved agents to treat AML, however, many patients relapse after achieving a response, underscoring the need for new therapies.

On November 19, 2024 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported third quarter 2024 financial results and provided a corporate update (Press release, Alpha Tau Medical, NOV 19, 2024, View Source [SID1234648496]).

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"Alpha Tau has continued to make great progress during 2024, with a number of important trials moving ahead and continued generation of data across superficial tumors and cancers of internal organs," said Alpha Tau Chief Executive Officer Uzi Sofer. "Our decision to use the ReSTART pivotal trial to explore our implementation of the Alpha DaRT treatment with community clinicians such as Mohs surgeons continues to bear fruit. We look forward to releasing important data in internal organ cancers in the coming months and giving our stakeholders a deeper look at the future we envision for the Alpha DaRT," stated Alpha Tau CEO Uzi Sofer.

Recent Corporate Highlights:

● In October, Alpha Tau announced its acceptance into FDA’s Total Product Life Cycle Advisory Program (TAP) to accelerate market access to Alpha DaRT for patients with recurrent glioblastoma multiforme (GBM). TAP’s primary goal is to expedite and enable patient access to innovative and highly promising medical devices which are not currently on the market by providing frequent, and strategic communications with the FDA, and by facilitating engagement with other key parties for developers of devices of public health importance, working toward reducing the time, cost and uncertainty of patient access through reimbursement and commercial adoption following FDA authorization.

● In October, the first patient with recurrent lung cancer was treated in a clinical trial at Hadassah Medical Center in Jerusalem, Israel. The study will assess safety and feasilibity of delivering Alpha DaRT sources into the lung using an endobronchial ultrasound (EBUS) procedure, including the rate of successful source placement and any treatment-related adverse events. For more information, please see here: View Source

● In September, the FDA approved and Investigational Device Exemption (IDE) application to initiate a multi-center study for the treatment of recurrent cutaneous Squamous Cell Carcinoma (cSCC) in immunocompromised patients using the Alpha DaRT. The clinical study, which is an investigator-initiated study led by the Winship Cancer Institute of Emory University in Atlanta, has been approved to enroll up to 28 U.S. patients at up to 8 institutions in the U.S., and will focus on patients with recurrent cSCC who have a weakened immune system due to any primary or secondary immunodeficiencies, excluding diabetes. For more information, please see here: View Source

Upcoming Milestones:

● Anticipating response from PMDA in Japan in Q1 2025 for pre-market approval for Alpha DaRT in patients with recurrent head and neck cancer.

● Planned release of data from pancreatic cancer trials in Canada and Israel in Q1 2025.

● Targeting completion of patient recruitment in the ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma in H1 2025. For more information, please see here: View Source

● Targeting release of data from combination trial of Alpha DaRT with pembrolizumab (Keytruda) in H1 2025. For more information, please see here: View Source

● Targeting first brain cancer treatment in H1 2025.

Financial results for quarter ended September 30, 2024

R&D expenses for the nine months ended September 30, 2024 were $19.5 million, compared to $18.9 million for the same period in 2023, due to increased employee compensation and benefits, including share-based compensation, increased costs of raw materials, reduced government grants, and increased travel expenses related to our U.S. multi-center pivotal trial, offset by lower third-party contractor expenses.

Marketing expenses for the nine months ended September 30, 2024 were $1.7 million, compared to $1.5 million for the same period in 2023, due to increased employee compensation and benefits.

G&A expenses for the nine months ended September 30, 2024 were $4.6 million, compared to $5.3 million for the same period in 2023, primarily due to decreased professional fees (including D&O insurance and legal expenses), offset by increased travel expenses and increased employee compensation and benefits, including share-based compensation.

Financial income, net, for the nine months ended September 30, 2024 was $3.5 million, compared to $4.0 million for the same period in 2023, due to changes in foreign exchange rates, a decrease in interest from bank deposits, and an increase in interest on long-term loan.

For the nine months ended September 30, 2024, the Company had a net loss of $22.3 million, or $0.32 per share, compared to a net loss of $21.8 million, or $0.31 per share, in the nine months of 2023.

Balance Sheet Highlights

As of September 30, 2024, the Company had cash and cash equivalents, short-term deposits and restricted deposits in the amount of $68.4 million, compared to $84.9 million at December 31, 2023. The Company expects that this cash balance will be sufficient to fund anticipated operations for at least two years.

About Alpha DaRT

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is designed to enable highly potent and conformal alpha-irradiation of solid tumors by intratumoral delivery of radium-224 impregnated sources. When the radium decays, its short-lived daughters are released from the sources and disperse while emitting high-energy alpha particles with the goal of destroying the tumor. Since the alpha-emitting atoms diffuse only a short distance, Alpha DaRT aims to mainly affect the tumor, and to spare the healthy tissue around it.