On May 23, 2024 Indapta Therapeutics, Inc., a privately held biotechnology company developing differentiated cell therapies for the treatment of cancer and autoimmune diseases, reported that CEO Mark Frohlich, MD, will be giving a plenary talk today titled, "g-NK cells for the treatment of cancer and autoimmune disease" at the New York Academy of Sciences Frontiers in Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) (Press release, Indapta Therapeutics, MAY 23, 2024, View Source [SID1234643667]).

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In his talk, Dr. Frohlich will summarize the differentiated mechanisms of target cell killing for Indapta’s lead clinical program, IDP-023, a g-NK cell therapy product. These mechanisms include highly robust antibody-dependent cell mediated cytotoxicity (ADCC), the targeting of HLA-E expressing cells via the NKG2C receptor, and the inherent anti-viral activity of g-NK cells. Indapta is currently applying g-NK cells to hematologic cancers in an ongoing Phase 1 trial enrolling patients with non-Hodgkin’s lymphoma, multiple myeloma and acute myelogenous leukemia.

Dr. Frohlich will also describe Indapta’s expanded focus on autoimmune disease, including its plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration for a clinical trial of IDP-023 in multiple sclerosis.

"Based on published evidence that endogenous g-NK cells are not only protective against the development of multiple sclerosis, but also slow the progression of the disease, we plan on filing an IND in mid-2024 to initiate a clinical trial of g-NK cells for this indication," said Dr. Frohlich. "In addition to being able to achieve B cell depletion by combining with a B cell directed monoclonal antibody, g-NK cells have additional mechanisms not shared by conventional NK cells or CAR-T cells, namely their ability to kill HLA-E expressing autoreactive T and B cells as well as address the Epstein Barr Virus reservoir that may contribute to the disease pathogenesis."

Indapta’s Differentiated g-NK Cell Therapy

Indapta’s universal, allogeneic NK cell therapy platform consists of a potent subset of naturally occurring NK cells, known as "g minus" NK cells, or "g-NK" cells. G‑NK cells arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). To generate IDP-023, Indapta preferentially expands g-NK cells from healthy donors, with low donor to donor variability.

Indapta’s g-NK can release dramatically more immune activating cytokines and cell-killing compounds than conventional NK cells. In preclinical studies, IDP-023 has demonstrated more potent and durable antitumor activity when combined with cancer targeting monoclonal antibodies as compared to conventional NK cells. (Bigley et al., Blood Advances 2021, View Source)

On May 23, 2024 Abdera Therapeutics Inc., a biopharmaceutical company leveraging its advanced antibody engineering ROVEr platform to design and develop tunable, precision radiopharmaceuticals for cancer, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for ABD-147, the first delta-like ligand 3 (DLL3) targeting radiopharmaceutical for the treatment of small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) (Press release, Abdera Therapeutics, MAY 23, 2024, View Source [SID1234643666]). Abdera plans to initiate a Phase 1 clinical trial in the second half of 2024.

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ABD-147 is a next-generation precision radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing DLL3. DLL3 is a protein found on the surface of neuroendocrine tumors, but rarely expressed on the surface of normal cells or tissues.

"ABD-147 represents a potential best-in-class treatment for SCLC and other aggressive neuroendocrine tumors," said Philippe Bishop, M.D., chief medical officer. "Leveraging our ROVEr platform, we custom-engineered ABD-147 with optimized pharmacokinetic properties and tumor penetration to destroy tumor cells while limiting radiation toxicity to the body. We are hopeful this highly potent next generation radiotherapeutic will provide a potential breakthrough addressing a critical medical need for the treatment of SCLC and other high-grade neuroendocrine cancers. We look forward to initiating a Phase 1 clinical trial of ABD-147 later this year."

The Phase 1, first-in-human, open-label clinical study aims to evaluate the safety and preliminary efficacy of 225Ac-ABD-147 in patients with SCLC or LCNEC who previously received platinum-based therapy. The study will determine the recommended dose regimen for future development.

"FDA clearance of our first IND marks a major milestone for Abdera as we transition into a clinical-stage radiopharmaceutical company," said Lori Lyons-Williams, president and chief executive officer. "We believe our ROVEr platform uniquely enables a new wave of innovation in targeted radiotherapeutics, with ABD-147 representing the first in a robust pipeline of custom-engineered programs we are advancing to the clinic."

About Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma

The global incidence for SCLC and LCNEC has been reported to represent approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., the incidence has been reported to be approximately 35,000 new cases annually. Fifteen percent of all lung cancer cases are high-grade neuroendocrine cancers. These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver and bone. Without treatment, the median survival from diagnosis has been reported to be only two to four months. With treatment, the overall survival at five years is 5% to 10% for SCLC, and 15% to 25% for LCNEC. SCLC and LCNEC generally carry a poor prognosis and new treatment options are urgently needed.

About ABD-147

ABD-147 is a targeted radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing delta-like ligand 3 (DLL3) with high affinity. DLL3 is a protein in the Notch pathway that is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. In certain high grade neuroendocrine carcinomas including small cell lung cancer (SCLC), DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases. In contrast, DLL3 is absent or very rarely expressed on the surface of nonmalignant cells. Given the high specificity of DLL3 expression on cancer cells and the distinct mechanism of action, DLL3 represents a compelling target for treating SCLC and other DLL3+ solid tumors with targeted radiotherapy.

About the ROVEr Platform

Abdera’s Radio Optimized Vector Engineering (ROVEr) platform enables the company to custom-engineer targeted radiopharmaceuticals with tunable pharmacokinetic (PK) properties to achieve high tumor uptake while minimizing renal exposure and mitigating other systemic radiotoxicities such as myelosuppression. Abdera can optimize the delivery and therapeutic index of potent radioisotopes capable of emitting powerful alpha or beta particles to selectively destroy tumor cells while sparing healthy cells, providing patients with potentially transformative new cancer treatments.

Abdera’s approach offers the ability to design radiotherapeutics against virtually any cancer target expressed on the cell surface. Coupled with a highly potent mechanism of cell killing, the ROVEr platform is uniquely poised to exploit both high- and low-expressing targets to selectively deliver therapeutic levels of radioisotope to cancer cells.

On May 23, 2024 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that it will present new data and offer expert perspectives on leading-edge cancer research and treatments in development at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, which will take place in Chicago from May 31 to June 4 (Press release, City of Hope, MAY 23, 2024, View Source [SID1234643665]). Highlights include the following:

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2024 Best of ASCO (Free ASCO Whitepaper) program: New data on mismatched unrelated donor peripheral blood stem cell transplantation
Late-breaking data on the phase 3 CodeBreaK 300 trial
Glofitamab monotherapy for patients with advanced mantle cell lymphoma
An oral inhibitor monotherapy for people with advanced kidney cancer
Interventions for older adults with cancer who traditionally have not had access to supportive care treatments that could improve quality of life
About 40,000 oncology professionals will attend the meeting, themed "The Art and Science of Cancer Care: From Comfort to Cure." City of Hope experts will have 64 presentations, including oral sessions, clinical science symposiums, education discussions and the following late-breaking abstract:

Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC)

Presenter: Marwan G. Fakih, M.D., City of Hope medical oncologist
Presentation Time and Location: Monday, June 3, 1:21 p.m. CT, Arie Crown Theater
Other noteworthy City of Hope abstracts:

Expanding access to stem cell transplants: Not a perfect match, yet perhaps just as good
Presentation Time and Location: Friday, May 31, 3:45 p.m. CT, S100bc

Access to potentially lifesaving stem cell transplants traditionally has been limited due to the need for a donor whose stem cells match the recipient’s genes. However, Monzr M. Al Malki, M.D., City of Hope hematologist-oncologist, co-led a multicenter phase 2 trial (NCT04904588) sponsored by NMDP and conducted via CIBMTR (Center for International Blood and Marrow Transplant Research) that demonstrates encouraging overall survival one year after older patients with advanced blood cancers received "HLA-mismatched unrelated donor peripheral blood stem cell transplantation," meaning the donor stem cells originated from someone who was not a relative and not a complete HLA match.

While the 13-site ongoing trial includes adults and children, this interim analysis that will be presented as an oral abstract presentation evaluated the first 70 older adult patients with advanced blood cancers who received this type of transplant and underwent both reduced intensity conditioning and post-transplant cyclophosphamide, which is a method used to prevent a potentially life-threatening side effect called graft-versus-host disease (GVHD). City of Hope has performed over 19,000 transplants, is one of the nation’s leading transplant programs and is at the forefront of using transplants to treat older adults with blood cancers.

Overall survival at one year post-stem cell transplant was 79%. Rates of GVHD and other complications were comparable to those of recipients who received HLA-matched donor stem cells, suggesting HLA-mismatched unrelated donor peripheral blood stem cell transplantation may one day be used more widely, expanding access to the lifesaving therapy.

"This data, supported by the National Marrow Donor Program, is promising and is the reason why I continue to work to expand access to stem cell transplantation for older patients, underrepresented people and patients with blood cancers," Dr. Al Malki said.

The adult cohorts of this trial recruitment have closed with more than 200 patients in follow-up. The pediatric arm of the trial is ongoing.

Bispecific antibody demonstrates sustained response rates in lymphoma patients who received and rejected previous treatments
Presentation Time and Location: Saturday, June 1, 5:24 p.m. CT, S100bc

In an updated efficacy and safety phase 1/2 trial (NCT03075696), bispecific antibody glofitamab continues to demonstrate compelling response rates with a fixed-duration treatment among a group of mantle cell lymphoma patients who have nearly exhausted approved treatment options due to aggressive disease.

The researchers evaluated close to 60 participants who had received two or more previous treatments — the majority of which had stopped responding to treatment before they enrolled in this study. Patients received about 7.4 months of glofitamab. Landmark analyses indicated that most patients with a complete response at the end of treatment were alive without disease progression 15 months after the end of treatment. The median duration of complete response was 12.6 months, and median progression-free survival was 8.6 months.

"People with mantle cell lymphoma have a rare form of non-Hodgkin lymphoma that is currently incurable, so it is encouraging to see people who were told by others that there is not much more to be done live months and even years longer with this treatment," said Tycel Phillips, M.D., City of Hope hematologist-oncologist and presenting author. "We at City of Hope continuously develop leading-edge treatments for people diagnosed with lymphoma and other blood cancers."

Early safety and clinical efficacy data on monotherapy DFF332 in advanced kidney cancer patients
Presentation Time and Location: Saturday, June 1, from 8:30 a.m. CT, S100bc

People with an advanced kidney cancer called clear cell renal cell carcinoma (ccRCC) appeared to experience positive medicinal effects from the targeted therapy pill DFF332 while encountering manageable side effects in an ongoing first-in-human phase 1/1B multicenter trial (CDFF332A12101, NCT04895748).

Sumanta "Monty" Pal, M.D., a City of Hope medical oncologist, will share preliminary data on 40 advanced kidney cancer patients who took DFF332, an oral hypoxia-inducible factor (HIF)-2α inhibitor that has been shown in preclinical models to be effective in reducing ccRCC tumors. All study participants had received at least one other type of therapy before joining the clinical trial. At data cutoff, 16 patients continued to be treated, while 19 patients (48%) stopped receiving the treatment due to disease progression. The most common side effects were fatigue (33%), anemia (30%), increased blood cholesterol and constipation (15%). No extreme adverse effects have been observed so far. At cutoff, 18 patients (45%) had stable disease and two patients (5%) achieved partial response.

"While the study is still in process, so far, we have seen a promising safety profile for monotherapy DFF332 with indications of clinical activity," Dr. Pal said. "We are conducting analysis on how the medicine moves within the body as well as collecting biomarker data that will be shared at our ASCO (Free ASCO Whitepaper) presentation."

Using telehealth to improve access to supportive care services for older adults with cancer living in lower-resourced communities
Presentation Time and Location: Saturday, June 1, at 1:39 p.m. CT, S102

A study at City of Hope | Antelope Valley found that telehealth can be leveraged to offer older adults living in high-poverty, lower resourced communities with a specialized evaluation developed at City of Hope called a geriatric assessment, which identifies supportive care services older adults with cancer need to manage vulnerabilities, better define care goals and improve quality of life.

This quality improvement study included 251 participants who were 65 years or older with newly diagnosed or advanced cancer. These patients underwent a baseline geriatric assessment and most had initial visits with a geriatric nurse practitioner – 197 via televideo and 45 via telephone. The assessment identified vulnerabilities in 209 patients and, after review, the nurse practitioner made 460 necessary referrals for supportive care services – 86% of which were implemented. The most common referrals were to pharmacy (177), social work (142), occupational therapy (76) and physical therapy (48). More than 92% of patients reported they were satisfied with the telehealth services that resulted in supportive care interventions for older adults.

"In my experience, if you don’t do a geriatric assessment, the patient pays for it later," said Tanyanika Phillips, M.D., M.P.H., presenting author and City of Hope medical oncologist and hematologist in Antelope Valley, California. Phillips noted that if care is prescribed without accurate health information, the result could be serious side effects or even hospitalization, which could lead not only to more costly care but also cancer treatment outcomes that are not the best for patients.

"In a general visit, patients often will say they feel well and are fine because they’re incentivized to answer in the affirmative and move forward with treatment," Phillips added. "Place this same patient in a different environment where they are answering geriatric assessment questions, and they may be more forthcoming and detailed about their lifestyle and abilities. This candor will help physicians prescribe the most appropriate care for that individual based on their circumstances."

Providing supportive care interventions via telehealth based on a geriatric assessment is shown to improve daily functioning, happiness and quality of life
Presentation Time and Location: Sunday, June 2, from 11:54 a.m. CT, S100bc

A randomized trial at a Brazilian cancer center and under the guidance of City of Hope’s internationally renowned cancer and aging expert William Dale, M.D., Ph.D., found that older adults with metastatic cancer reported experiencing significant improvements in the performance of daily activities, emotional well-being and quality of life after receiving a telehealth-based geriatric assessment (GA) that resulted in supportive care interventions. This data extends City of Hope’s prior work in GA-guided supportive care beyond the borders of the United States.

"Our studies continue to prove that patients and families win when care teams ask older adults with cancer the right questions at the outset to guide care. This is true even when telehealth is used in a low-resource environment. Guidance from a GA can change care choices and improve outcomes — all without making cancer therapy less effective. It’s a form of precision medicine: more appropriate supportive care interventions, better daily functioning, higher quality of life and the same great cancer care results. It’s a winning formula for patients, families, providers and the health system," said Dr. Dale, senior author of the study, City of Hope’s George Tsai Family Chair in Geriatric Oncology and director of City of Hope’s Center for Cancer and Aging. Dr. Dale is the recipient of this year’s B.J. Kennedy Geriatric Oncology Award, which honors geriatric oncologists who have demonstrated outstanding leadership and achievement in the field of geriatric oncology.

Additional highlights include the following award-winning poster abstract and three education sessions:

"A phase I/II trial of palbociclib, pembrolizumab, and endocrine therapy for patients with HR+/HER2- locally advanced or metastatic breast cancer (MBC): Clinical outcomes and stool microbial profiling"*
Presentation Time: Sunday, June 2, from 9 a.m. to noon CT
Presenter: Alexis LeVee, M.D., City of Hope Hematology & Medical Oncology Chief Fellow
*Conquer Cancer, the ASCO (Free ASCO Whitepaper) Foundation, awarded Dr. LeVee a 2024 ASCO (Free ASCO Whitepaper) Annual Meeting Merit Award, which supports students and trainees who are first authors on abstracts selected for presentation.
"Evidence Evaluating Cannabis’ Efficacy Across the Cancer Care Continuum"
Monday, June 3, 8:30 a.m. CT
Session title: Evidence-Based Integrative Oncology: Guideline Insights for Comprehensive Care
Presenter: Richard T. Lee, M.D., City of Hope clinical professor, Supportive and Integrative Medicine Program; Cherng Family Director’s Chair for the Center for Integrative Oncology
"Tissue-Based Molecular Testing and the Role of Artificial Intelligence"
Monday, June 3, 10 a.m. CT
Session title: Should I Order the Test? Expanding the Array of Emerging Diagnostics in Breast Cancer
Presenter: Daniel Schmolze, M.D., City of Hope associate clinical professor, Department of Pathology
"What Is Variant Histology Renal Cell Cancer and What Are the Available Treatment Options?"
Monday, June 3, 3:15 p.m. CT
Session title: Managing Variant Histologies in Urothelial and Renal Cell Cancers
Presenter: Sumanta Kumar Pal, M.D., City of Hope professor, Department of Medical Oncology & Therapeutics Research

On May 23, 2024 Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, reported a poster presentation highlighting the ongoing Phase 1 study of IAM1363, a selective and brain-penetrant inhibitor of HER2 signaling for the treatment of HER2-driven cancers (Press release, Iambic Therapeutics, MAY 23, 2024, View Source [SID1234643664]). The TIP (trials in progress) poster will be shared at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place May 31-June 4 in Chicago.

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IAM1363 is a small molecule inhibitor of wild-type and oncogenic mutant HER2 proteins, designed to expand the therapeutic index compared to available HER2 inhibitors and to avoid toxicities from off-target inhibition of EGFR. In preclinical studies, IAM1363 has demonstrated over 1000-fold selectivity for HER2 compared to EGFR, a promising pharmacokinetic and safety profile, preferential tumor enrichment, and penetrance of the central nervous system. In HER2 tumor models, including intracranial tumor models, IAM1363 has demonstrated favorable efficacy and tolerability compared to benchmark tyrosine kinase inhibitors and HER2-targeted antibody-drug conjugates. IAM1363 was identified using Iambic’s AI-driven discovery platform and is now being evaluated in a Phase 1 clinical study, IAM1363-01 (NCT06253871).

Poster Presentation Details:

Title: IAM1363-01: A phase 1/1b Study of a Selective and Brain-Penetrant HER2 inhibitor for HER2-driven Solid Tumors

Abstract Number: TPS3186

Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Location: Hall A, Poster board 318a

Date and Time: June 1, 9:00am-12:00pm CT

Presenter: Alex A. Adjei, MD, PhD, FACP, Chief of the Cleveland Clinic’s Cancer Institute

On May 23, 2024 Xspray Pharma AB (publ) (Nasdaq Stockholm: XSPRAY), a Swedish pharmaceutical company which uses its innovative Hynap technology to develop 505(b)(2) improved versions of marketed drugs for the treatment of cancer reported the online publication of its abstract titled "Frequency of Comedication of Proton Pump Inhibitors with Crystalline Dasatinib in Chronic Myeloid Leukemia and Effects on TKI-Bioavailability" for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on June 3rd, 2024 at 9-12 AM, Poster nr. 120 (1) (Press release, Xspray, MAY 23, 2024, https://www.businesswire.com/news/home/20240523850369/en/Xspray-to-present-data-at-ASCO-highlighting-frequent-comedication-of-PPIs-with-TKIs-in-CML-patients-and-greater-than-expected-negative-effects-on-the-bioavailability-of-crystalline-dasatinib [SID1234643663]).

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While Tyrosine Kinase Inhibitors (TKI), including dasatinib, have profoundly improved clinical outcomes in patients with chronic myeloid leukemia (CML), the bioavailability and systematic exposure of the crystalline formulation of dasatinib is reduced by comedication with acid reducing agents which may affect the clinical response and comedication with proton pump inhibitors, such as omeprazole, should be avoided (2).

The collaborative analysis with Uppsala University and the Karolinska Institute and University Hospital demonstrates that 54% of CML patients identified in the Swedish CML-register were prescribed at least one PPI and 34% of TKI-treated patients were comedicated with a PPI. Of those prescribed a PPI, 66% of the prescriptions were by a different healthcare provider. Further, the presentation provides new information on the bioavailability of crystalline dasatinib when comedicated with a PPI, demonstrating a substantially higher than previously reported impact of PPIs on the bioavailability of crystalline dasatinib, with Cmax and AUC24 being reduced by 96% and 88% respectively.

"Consistent absorption and bioavailability of dasatinib are critical for adequate disease control and patient outcomes, this is however often overlooked in clinical practice as our data demonstrates," said Per Andersson, CEO of Xspray. "To address this important issue, we are on track to launch Dasynoc, our optimized version of dasatinib, with a Prescription Act Use Fee Amendment date (PDUFA-date) of 31st of July 2024 and the US commercial launch of Dasynoc on 1st September 2024."

The abstract is now available online at View Source

References:

Dahlén T, Larfors G, Lennernäs H et al. Frequency of Comedication of Proton Pump Inhibitors with Crystalline Dasatinib in Chronic Myeloid Leukemia and Effects on TKI-Bioavailability. American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), Annual Meeting 2024. Chicago. Abstract 6561. Poster 120. View Source
Sprycel (dasatinib) Tablets for oral use. Labeling, Supplement 27. 02 Aug 2023. View Source;ApplNo=021986. Accessed 22 May 2024.