On December 12, 2023 Ankyra Therapeutics, an emerging clinical-stage biotechnology company pioneering anchored immunotherapies to treat cancer, reported results from a preclinical study demonstrating potent anti-tumor activity of its lead program ANK-101 were published in the December issue of the Journal of Clinical Investigation Insight (JCI Insight) (Press release, Ankyra Therapeutics, DEC 12, 2023, View Source [SID1234638518]). The research paper is titled "Intratumoral aluminum hydroxide-anchored IL-12 drives potent antitumor activity by remodeling the tumor microenvironment."

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ANK-101 is a novel tumor-directed anchored immune medicine (AIM) composed of interleukin-12 (IL-12) linked to aluminum hydroxide.

"One of the key challenges of intratumoral administration is retention within the tumor, both for efficacy and to limit systemic exposure," said Howard L. Kaufman, M.D., President and Chief Executive Officer of Ankyra Therapeutics. "Our pre-clinical data indicates that anchored immunotherapy retains active IL-12 at the tumor site for weeks, versus just hours with unanchored recombinant IL-12. This results in potent immune activation with limited systemic exposure, indicating the potential to improve patient outcomes while reducing side effects. We are excited to continue to advance this program and look forward to initiating our Phase 1 clinical study in humans in early 2024."

Data published in JCI showed:

Ankyra’s anchored immunotherapy platform achieves retention of the drug ANK-101 at the injected site for approximately four weeks
One or two intratumoral injections of a murine ANK-101 analogue induced single-agent anti-tumor activity across a diverse range of syngeneic mouse models
Local treatment with the drug induced tumor regressions of distant, non-injected lesions demonstrating abscopal effects, which were enhanced when combined with systemic checkpoint blockade
Anti-tumor activity mediated by the drug was associated with recruitment of immune cells and remodeling the tumor microenvironment
Human ANK-101, when tested in cynomolgus macaques, was well tolerated
About ANK-101
ANK-101 is an anchored drug complex composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks, but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents.

On December 12, 2023 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that 23% of patients with relapsed or treatment-resistant KMT2Ar AML, ALL and mixed phenotype leukemia who took revumenib in the AUGMENT-101 multicenter clinical trial had a complete remission (CR) — the cancer went into remission with complete recovery of peripheral blood counts — or a CRh — the cancer went into remission and there was partial recovery of peripheral blood counts (Press release, City of Hope, DEC 12, 2023, View Source [SID1234638517]). The data was presented as a late-breaking abstract at ASH (Free ASH Whitepaper) and in a press briefing. Revumenib is a highly selective inhibitor of the menin-KMT2A binding interaction that is being developed by Syndax Pharmaceuticals.

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"We look forward to submitting a new drug application to the U.S. Food and Drug Administration for revumenib for the treatment of R/R KMT2Ar acute leukemia by year-end, with the goal of efficiently bringing this treatment to patients who need it most."

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These 13 patients with CR or CRh also stayed in remission for an average of 6.4 months, with six patients still remaining in remission at the time the data was collected. Trial participants had an overall response rate (ORR) of 63%, or 36 out of 57 patients, meaning they had a partial or complete clearance of the leukemia in response to the therapy with or without blood count recovery.

"The only current treatment plan for adult and pediatric patients with these types of relapsed or treatment-resistant leukemias is chemotherapy to achieve temporary remission as a path to a bone marrow or stem cell transplant. But fewer than 10% of these patients respond to the chemotherapy, and the expectation for survival is in the range of three months," said Ibrahim Aldoss, M.D., City of Hope associate professor in the Division of Leukemia within the Department of Hematology & Hematopoietic Cell Transplantation and principal investigator for the AUGMENT-101 trial. "What this trial demonstrates is that revumenib did work safely and effectively in varying degrees in a majority of trial participants and had induced deep remissions in the majority of responders, giving us hope about the prospect of an additional, urgently needed treatment option, as well as a therapy that can help these patients to receive a curative bone marrow or stem cell transplant."

Thirty-nine percent of patients who had ORR, or 14 total, were able to successfully receive a bone marrow or stem cell transplant — the only treatment that can cure these leukemia types — while their cancer was in remission with the therapy. Aldoss explained that this finding is important since patients with these leukemias cannot have a transplant if their bone marrow continues to have disease. In addition, half of transplanted patients took revumenib after a transplant as a maintenance therapy to reduce the chance of leukemia relapsing.

The study enrolled 92 patients with KMT2Ar leukemias, including children, adults and older adults, with various leukemia subtypes (AML, ALL and mixed phenotype leukemia). Fifty-seven patients in the largest group had their KMT2Ar finding confirmed by a central laboratory, and they were considered for the study’s efficacy endpoint.

"We are thrilled to present additional detail on the positive results for revumenib in KMT2Ar acute leukemia that continue to demonstrate its consistently compelling clinical profile as a potential monotherapy for these heavily pretreated patients with high unmet need," said Michael A. Metzger, chief executive officer of Syndax. "We look forward to submitting a new drug application to the U.S. Food and Drug Administration for revumenib for the treatment of R/R KMT2Ar acute leukemia by year-end, with the goal of efficiently bringing this treatment to patients who need it most."

Aldoss noted that revumenib produced comparable response rates in patients of different ages and leukemia subtypes.

Tatum Demontmorency, 19, participated in the clinical trial at City of Hope after she was diagnosed with leukemia in 2021. The Bakersfield, California, resident began to feel weak and fatigued, and at first, doctors suspected a viral infection like mononucleosis. Demontmorency later started to experience severe stomach pain.

After more bloodwork and a computed tomography (CT) scan, she was diagnosed with AML with KMT2Ar. She was treated with standard chemotherapy, but unfortunately her leukemia returned later. Demontmorency and her family were advised to travel to Los Angeles for cancer treatment, and she eventually sought care at City of Hope’s Children’s Cancer Center, where she enrolled in the revumenib trial. The therapy, an oral pill that is taken twice a day in a 28-day cycle, cleared all her detectable cancer, and Demontmorency was able to receive a stem cell transplant from her brother, Trey.

Demontmorency is now a sophomore at Bakersfield College, has her eye on a career in health care, possibly as an ultrasound technician, and has returned to playing volleyball. She also coaches the team at her old high school.

"Tatum’s story is truly inspirational, and our hope is that revumenib will continue to make it possible for our patients with these types of leukemias to continue with their lives," Aldoss added.

Among trial participants, the therapy was safe and tolerable, with the most common side effects of nausea, differentiation syndrome and reversible changes in electrocardiogram. Patients tolerated these and other side effects well as only 6% of patients left the trial due to treatment-related adverse effects.

If approved for use by the FDA, the product would be the first therapy to target what’s known as the menin-KMT2A interaction. Menin is a protein that binds to KMT2A, a genetic defect, and this interaction causes KMT2Ar AML and ALL to accumulate abnormal cells in the bone marrow and blood. Revumenib can prevent this interaction from occurring, leading to possible cancer remission.

On December 12, 2023 SimBioSys, a TechBio company unlocking the power of spatial biophysics with artificial intelligence (AI) and data science to redefine precision medicine for cancer with software tools, reported new data from its TumorSight and PhenoScope platforms at the 46th Annual San Antonio Breast Cancer Symposium (SABCS), held from December 5-9, 2023 (Press release, SimBioSys, DEC 12, 2023, View Source [SID1234638516]).

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Data from both internal and external validation studies were shared in six separate poster presentations at the conference. The results included collaborations with top cancer research institutions, multi-institutional analysis, enhanced visualization, and volumetric prediction capabilities to aid surgical planning.

"We were thrilled to share these exciting data with the broader breast cancer research community, which are a testament to the utility of our first of its kind digital diagnostic & treatment planning platforms, TumorSight and PhenoScope, to support a patient’s end-to-end journey in their battle against cancer," said Tushar Pandey, Chief Executive Officer at SimBioSys. "We also extend our gratitude toward our incredible collaborators and look forward to expanding our research partnerships and in the near future supporting their clinical care."

The presentations and key findings are shared below and can also be found on the SimBioSys website.

(PO2-01-01) Biophysical Simulation Using DCE-MRI to Forecast Response to NAT in HER2+ Patients, with Glucose Characterization and Orthogonal Validation Using FDG-PET.

Collaborators: City of Hope, Oregon Health & Sciences University

Research Summary: We conducted 3D biophysical simulations of individual HER2+ breast cancer patients to forecast responses to neoadjuvant chemotherapy (NAT).

Key Findings:

SimBioSys’ biophysical simulations of HER2-targeted therapy accurately predicted patient response, yielding predictive accuracy of 0.83.
Further, our team was able to characterize the performance by showing correlation of the perfusion maps, constructed from the 3D biophysical simulations on patient DCE-MRI, with two PET modalities that are representative of the tumor microenvironment.
This novel approach could be used in both the research and clinical settings, offering actionable information on what drives patient-specific therapeutic response for more individualized care.
(PO2-02-11) Radiomics and an Erosion Model to Predict Post-Neoadjuvant Therapy Tumor Characteristics for Personalized Breast Cancer Treatment.

Collaborators: Northwestern Medicine, University of North Carolina, Baylor Scott & White

Research Summary: We used pre-treatment imaging data to accurately predict neoadjuvant therapy (NAT) effectiveness.

Key Findings:

The predicted tumors clinically relevant characteristics (tumor volume, convex hull volume, and morphological/spatial characteristics) showed close agreement with post-NAT imaging ground truth.
By providing reliable estimates of post-NAT tumor characteristics using SOC pre-NAT data, this predictive model could enable personalized treatment planning and patient stratification to optimize patient care.
(PO1-01-05) Spatial PK/PD Model with HER2 Expression for Predicting Individual Tumor Response to TDM1.

Research Summary: We developed a spatial PK/PD model for the antibody-drug conjugate trastuzumab emtansine (T-DM1) and explored the relationship between HER2 target expression and other tumor microenvironment features.

Key Findings:

SimBioSys’ spatial PK/PD analyses improve prognostic predictions compared to HER2 gene expression data alone.
The spatial biophysical model demonstrated that features of the spatial tumor microenvironment also influence response in addition to target expression.
(PO2-02-10) Predicting the Feasibility of Breast Conserving Surgery Using Pre-treatment Standard of Care DCE-MRI: A Novel Clinical Decision Support Tool for Breast Cancer Surgical Planning.

Collaborators: University of Chicago, University of Alabama, Mayo Clinic, Northshore Health

Research Summary: We developed a tool capable of providing informed recommendations on breast conserving surgery (BCS) or mastectomy based on standard of care imaging patient data.

Key Findings:

TumorSight successfully predicted BCS in 76% of cases, and mastectomy in 61%.
TumorSight and the BCS Feasibility Score help empower both patients and clinicians with information and tools to facilitate surgical planning decisions.
(PO2-07-04) Applying the Alliance Trial Guidelines in Multi-focal Breast Disease Using an Artificial Intelligence Computational Platform: Economic Analysis and Cosmetic Sensitivity.

Collaborators: Mayo Clinic, University of Cincinnati, University of Chicago, Baylor College of Medicine

Research Summary: We evaluated a patient cohort to better understand the economic impact of the Alliance trial and further categorize patients that would most benefit without suffering cosmetic impact.

Key Findings:

Our economic analysis of BCS vs. mastectomy revealed an estimated $17,000-$28,500 cost savings for BCS patients with private insurance, suggesting that both decreased costs and improved quality-of-life can be mutually aligned.
We estimated that BCS conversion from mastectomy offers to provide a net savings of $170-350 million annually.
(PO2-03-01) Personalized 3D Tumor Models Drive Shared Decision-making in Early Breast Cancer.

Collaborators: Patient Advocates in Research, Dana-Farber Cancer Institute

Research Summary: Early breast cancer Patient Opinion Leaders (POLs) and surgeons were surveyed to assess TumorSight’s potential impact on shared decision making for breast cancer surgical options.

Key Findings:

POLs and surgeons showed positive reception to TumorSight visualization for surgical planning and decision-making.
POLs noted that many patients don’t know that they have a choice in surgery.
90% of POLs believed visualization is very important to early breast cancer patients, and 80% believed it will increase confidence in their decisions and in their surgeon.
Computational tools such as TumorSight may facilitate patient understanding and improve patient-tailored treatments.

On December 12, 2023 Quanterix Corporation (NASDAQ: QTRX), a company fueling scientific discovery through ultrasensitive biomarker detection, reported that President and Chief Executive Officer Masoud Toloue will present at the 42nd Annual J.P. Morgan Healthcare Conference (Press release, Quanterix, DEC 12, 2023, View Source [SID1234638515]). Quanterix’s session will take place on Wednesday, January 10, 2024, at 5:15 p.m., PST.

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Webcast Information

The live webcast presentation can be accessed here and from the Investors section of the company’s website at www.quanterix.com. A replay of the webcast will be available for a limited period following the conference.

To learn more about Quanterix, visit www.quanterix.com/company. To learn more about Quanterix’s Simoa technology, visit www.quanterix.com/simoa-technology.

On December 12, 2023 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting, the Company presented one poster with study results for zevorcabtagene autoleucel ("zevor-cel", R&D code: CT053, an autologous CAR T-cell therapy candidate against BCMA), which include the 3-year follow-up on efficacy and safety results from the Phase I portion of Phase I/II registrational study in China (LUMMICAR-1, NCT03975907) (Press release, Carsgen Therapeutics, DEC 12, 2023, View Source [SID1234638513]). Details are listed below:

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Poster #4845: Three-Year Follow-up on Efficacy and Safety Results from Phase I LUMMICAR Study 1 of Zevorcabtagene Autoleucel in Chinese Patients with Relapsed or Refractory Multiple Myeloma

Zevor-cel is a fully human autologous chimeric antigen receptor (CAR) T-cell therapy product against B-cell maturation antigen (BCMA) which is being developed for the treatment of patients with relapsed or refractory multiple myeloma (R/R MM).

The LUMMICAR STUDY 1 trial is a multi-center, open-label Phase I/II clinical trial ongoing in China. The New Drug Application (NDA) in China for zevor-cel is based on the Phase I/II data from LUMMICAR STUDY 1 and is currently under review.

Herein, the Company presented the updated results with 3 years of follow-up after the last patient was infused with zevor-cel in the Phase I portion of the study. Responses were assessed by investigator per the International Myeloma Working Group (IMWG) 2016 criteria.

As of July 17, 2023, 14 participants with R/R MM, who had received at least 3 prior regimens including a proteasome inhibitor and an immunomodulatory drug (IMiD) with a median of 6 prior regimens (range: 3-11), received zevor-cel infusion. A single infusion of zevor-cel was administered 1-2 days after the completion of lymphodepletion. Three participants received 1.0×108 CAR+ T cells, and 11 participants received 1.5×108 CAR+ T cells. The median age of the cohort was 54 years (range: 34-62 years); 50.0% (7/14) of the participants had high-risk cytogenetic abnormalities, 14.3% (2/14) had extramedullary disease (EMD), and 14.3% (2/14) of the participants had Stage III disease based on International Staging System (ISS).

Safety
Overall, the safety profile of zevor-cel was manageable. There were no ≥ Grade 3 cytokine release syndrome (CRS) events. There were no immune effector cell-associated neurotoxicity syndrome (ICANS) events of any grade. Three treatment-related Grade 3 infections were observed. Three patients experienced serious adverse events (SAE) including 2 patients who had treatment-related SAEs which were pulmonary infection and tumor lysis syndrome. There were overall 2 deaths on the study; neither was related to zevor-cel.

Efficacy
As of July 17, 2023, the median follow-up duration was 37.7 months (range:14.8-44.2 months). The overall response rate (ORR) was 100% (14/14) with 78.6% (11/14) patients achieving a complete response (CR) or a stringent complete response (sCR); minimal residual disease (MRD) negativity was attained in all patients achieving either a CR or sCR. The median duration of response (mDOR) was 24.1 months in all patients and 26.0 months in those achieving CR or sCR. The median progression-free survival (mPFS) was 25.0 months. A total of 7 (50%) patients were in remission lasting longer than 24 months. The median overall survival (OS) was not reached, and 92.9% (13/14) of patients were still alive at month 36.

Conclusion
At 3-year follow up of Phase I portion of LUMMICAR-1 study in heavily pre-treated R/R MM population, zevor-cel demonstrated an encouraging safety profile with deep and durable responses consistent with the initial results.

About Zevor-cel
Zevor-cel (CT053) is a fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. The New Drug Application (NDA) for zevor-cel is based on the Phase I/II data from LUMMICAR STUDY 1 in China and is currently under review. CARsgen is conducting a Phase 1b/2 LUMMICAR STUDY 2 clinical trial in North America to evaluate the safety and efficacy of zevor-cel for R/R MM.

Zevor-cel received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. FDA in 2019, as well as Priority Medicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020, respectively. Zevor-cel also received Breakthrough Therapy designation from the NMPA in 2020.