On May 21, 2024 Indapta Therapeutics, Inc., a privately held biotechnology company developing next-generation differentiated cell therapies for the treatment of cancer and autoimmune diseases, reported that Cancer Prevention and Research Institute of Texas (CPRIT) has granted the company a competitive product development research award (Press release, Indapta Therapeutics, MAY 21, 2024, View Source [SID1234643513]). The $4.5 million grant will support Indapta’s ongoing clinical development of its lead product, IDP-023, for patients with advanced non-Hodgkin’s lymphoma and multiple myeloma.

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"We greatly appreciate that CPRIT has recognized the promise of Indapta’s allogeneic g-NK cell therapy for the treatment of advanced cancer patients," said Dr. Mark Frohlich, CEO of Indapta. "We are highly encouraged to be seeing early evidence of clinical activity in the safety run-in portion of the trial at the lowest cell dose and without the addition of a monoclonal antibody. We look forward to using the CPRIT funds to treat additional patients in order to reach clinical proof-of-concept in our Phase 1 dose escalation trial."

Patients enrolled in the Phase I clinical trial to date have received up to three planned doses of IDP-023 with or without interleukin-2. Once safety of multiple doses in combination with interleukin-2 has been established, cohorts of patients with lymphoma and multiple myeloma will receive escalating doses of IDP-023 in combination with the monoclonal antibodies, rituximab and daratumumab, respectively.

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. IDP-023 has several differentiated mechanisms of killing target cells without the need for genetic engineering, including 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’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)

Based on evidence that endogenous g-NK cells are protective against the development of multiple sclerosis, as well as slow disease progression in patients with multiple sclerosis, Indapta plans to file an IND in Q3 to initiate a clinical trial of g-NK cells in patients with multiple sclerosis.

On May 21, 2024 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported certification for its Guardant360 CDx blood test under the European Union’s In Vitro Diagnostic Regulation (IVDR 2017/746) (Press release, Guardant Health, MAY 21, 2024, View Source [SID1234643512]). The certification from TÜV SÜD Product Service is for tumor mutation profiling in patients with any solid cancerous tumor and for companion diagnostic indications to identify patients who may benefit from certain targeted therapies for advanced non-small cell lung cancer and breast cancer.

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Under the previous EU regulatory framework (IVD Directive 98/79/EC), manufacturers were able to self-certify most of their molecular assays. Under the IVDR most must obtain a conformity assessment and certificate from an accredited company, called a notified body, such as TÜV SÜD. Guardant360 CDx is a next generation sequencing (NGS)-based assay that detects genomic alterations using circulating tumor DNA from blood. The test allows clinicians to use tumor mutation profiling, also known as comprehensive genomic profiling (CGP), to identify somatic mutations in solid tumors from a simple blood draw to inform personalized treatment decisions for their patients with advanced cancer.

"The IVDR certification for the Guardant360 CDx liquid biopsy is a significant milestone for cancer care in the EU, as the test provides faster access to comprehensive genomic profiling for oncologists and, more importantly, for the patients they treat," said Helmy Eltoukhy, Guardant Health chairman and co-CEO. "We are confident that this certification will help accelerate wider adoption of guideline-recommended genomic profiling, pave the way for the development of new targeted therapies, and increase the number of advanced cancer patients who receive potentially life-changing treatments."

More than 1.2 million people are predicted to die from cancer in the EU in 2024,1 many of whom could benefit from comprehensive genomic profiling to guide a more personalized treatment plan, based on the growing availability of effective CGP-informed targeted therapies. Clinical studies show that patients receiving targeted therapies have improved progression-free survival and higher overall response rates relative to chemotherapy or immunotherapy.2-8

"Clinical adoption of targeted therapies lags behind medical guidelines due to several factors, including insufficient tissue for molecular profiling, which is the case for as many as 30 percent of solid cancer patients," said Nicola Normanno, MD, scientific director of IRCCS Romagna Institute for the Study of Tumors (IRST) "Dino Amadori" in Meldola, Italy.9-11 "Expanding the use of genomic profiling with IVDR-certified liquid biopsy will help the cancer care community establish more clinically relevant biomarkers to improve diagnosis and quickly identify the personalized therapies that patients can benefit from."

Under the IVDR, Guardant360 CDx is certified as a companion diagnostic to identify patients with non-small cell lung cancer who may benefit from treatment with TAGRISSO (osimertinib), RYBREVANT (amivantamab), or LUMYKRAS (sotorasib), and advanced breast cancer patients with ESR1 mutations who may benefit from treatment with ORSERDU (elacestrant).

Personalized medicines such as these have been life-changing for many cancer patients who have targetable mutations and are thus most likely to benefit from a particular therapy. IVDR certification for Guardant360 CDx is significant because it ensures continued broad access in the EU to comprehensive genomic profiling, which plays a critical role in helping biopharma companies identify patients to enroll in clinical trials and helping oncologists match patients to new precision medicines that target solid tumors.

"I am pleased that the new IVDR framework provides strict and high quality standards for diagnostic tools, because this will contribute to better standard of care and clinical trial protocols," said Peter Fasching, MD, professor of Obstetrics and Gynecology and coordinator of the Breast Cancer Center and the Gynecological Cancer Center at the Comprehensive Cancer Center Erlangen-EMN, Germany. "Using IVDR-certified liquid biopsy more broadly will allow us to find more biomarkers that can be targeted in the future and gives clinicians confidence that they are using a highly validated tool to select the optimal individualized treatment plan for the patient."

Since being introduced, the Guardant360 test has become widely accepted for blood-based comprehensive genomic profiling, with more than 400 peer-reviewed publications. It has been used by more than 12,000 oncologists, with more than 500,000 tests performed to date.

About Guardant360 CDx

The first FDA-approved blood test for complete genomic testing, Guardant360 CDx received U.S. FDA approval in August 2020 and CE mark for tumor mutation profiling in March 2021. For oncologists, the test provides comprehensive genomic results from a simple blood draw in seven days, helping them move beyond the limitations of tissue biopsies to rapidly obtain clinically relevant information in time to match patients to the optimal personalized treatment. Guardant360 CDx covers all genes recommended by the National Comprehensive Cancer Network, including those most relevant to clinical care and NSCLC treatment guidelines. For more information, visit guardant360cdx.com.

On May 21, 2024 Qurient Co. Ltd. (KRX: 115180), a clinical-stage biotech company based in Korea, reported to have entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI), part of the National Institutes of Health (NIH), to evaluate Qurient’s proprietary CDK7 inhibitor, Q901, in combination with an antibody drug conjugate (ADC) targeting tumor-associated calcium signal transducer 2 (TROP2) with topoisomerase 1 inhibitor payload for the treatment of small cell lung cancer (SCLC) and other relapsed solid tumors (Press release, Qurient Therapeutics, MAY 21, 2024, View Source [SID1234643511]).

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Q901 is a highly selective CDK7 inhibitor under Phase 1/2 clinical development in the United States and South Korea. Qurient demonstrated Q901’s main mechanism of action as transcriptional inhibition of essential genes for tumor progression, including genes involved in DNA damage repair response, which led to strong synergy with a topoisomerase 1 inhibitor (Ref: DOI: 10.1158/1538-7445.AM2024-5712). These results are consistent with prior findings from Dr. Anish Thomas’ team at NCI, which revealed a synergistic mechanism between CDK7 inhibition and topoisomerase 1 inhibition (Ref: DOI: 10.1158/1535-7163.MCT-21-0891).

Under this CRADA, NCI and Qurient will collaborate on an NCI-sponsored Phase 1/2 clinical study of Q901 in combination with the TROP2-ADC in SCLC and other relapsed solid tumors, starting from combination dose escalation and evaluating the safety, efficacy, and potential synergy of this novel combination. This collaboration is focused on development and evaluation of this innovative therapy for patients with extensive stage SCLC.

"The collaboration between the NCI and Qurient is based on the science discovered through independent research conducted by each institution," said Kiyean Nam, Ph.D., CEO of Qurient. "We hope the new combination therapy will help patients with small cell lung cancer, where current therapeutic options are limited."

About Q901

Q901 is a highly selective covalently binding small molecule CDK7 inhibitor under Phase 1/2 clinical development. Q901 demonstrated strong tumor growth inhibition in multiple cancer models including HR+ breast cancer, pancreatic cancer, prostate cancer, ovarian cancer, and small cell lung cancer as a single agent, as well as in combination with other therapies. Q901 in combination with fulvestrant is in a clinical trial for HR+ breast cancer patients who are refractory to CDK4/6 inhibitor and estrogen therapy combination.

On May 21, 2024 Dragonfly Therapeutics, Inc., a clinical stage biotechnology company developing novel immunotherapies, reported that it has entered into a clinical collaboration with Merck (known as MSD outside the US and Canada), to evaluate DF9001, Dragonfly’s EGFR immune engager, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with advanced solid tumors expressing EGFR (Press release, Dragonfly Therapeutics, MAY 21, 2024, View Source [SID1234643510]).

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"Merck, a trusted leader in drug development, has been a wonderful collaborator with Dragonfly since we signed our first collaboration agreement in 2018," said Bill Haney, co-founder and CEO of Dragonfly Therapeutics. "We are pleased to enter into this agreement with Merck for our ongoing, investigational Phase 1 trial of DF9001. In preclinical models, DF9001 engages multiple immune effector cells to drive anti-tumor activity and induces PD-L1 expression in tumor cells, sensitizing cold tumors to checkpoint inhibitors. We are hopeful that DF9001 in combination with KEYTRUDA will drive potent anti-tumor activity in a broad range of indications and are excited to further accelerate progress in the clinic to benefit patients in need."

Dragonfly is the study sponsor and first patients are expected to receive DF9001 in combination with pembrolizumab in Q4 2024. Clinical trial sites are currently open for monotherapy dosing in the U.S., with additional sites in North America and Europe expected to open in 2024. Additional information about the trial, including eligibility criteria, can be found at: View Source (ClinicalTrials.gov Identifier: NCT 05597839).

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About DF9001
DF9001 is an investigational first-in-class multi-specific drug candidate that targets EGFR and potently redirects natural killer (NK) cells, gamma-delta T cells, and CD8 T cells by engaging activating receptors NKG2D and CD16. DF9001 was discovered and developed using Dragonfly’s TriNKET platform. DF9001 is being evaluated in adult patients for the treatment of advanced solid EGFR-positive tumors. DF9001 has the potential to stimulate anti-tumor immunity in patients who are not eligible or not adequately responding to current therapies. DF9001 is the second wholly owned drug candidate in a pipeline of TriNKETs that Dragonfly is developing to address high unmet needs for patients across a broad range of disease areas.

On May 21, 2024 Ractigen Therapeutics, a pioneering developer of small activating RNA (saRNA) therapeutics, proudly reported that its flagship program, RAG-01, has been granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) (Press release, Ractigen, MAY 21, 2024, View Source [SID1234643509]). This notable achievement marks a significant milestone in the advancement of saRNA technology and underscores Ractigen’s commitment to addressing critical unmet medical needs. The milestone establishes RAG-01 as the first saRNA drug worldwide to achieve FTD.

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RAG-01 is currently undergoing a Phase I clinical trial in Australia for the treatment of non-muscle invasive bladder cancer (NMIBC). The trial, initiated in December 2023, has successfully enrolled and dosed three patients, demonstrating the program’s progress in clinical development.

FDA’s recent approval of the Investigational New Drug (IND) application for RAG-01 further validates the therapeutic potential of this innovative saRNA therapy. This regulatory milestone not only paves the way for the expansion of clinical trials in the United States but also highlights the FDA’s recognition of RAG-01’s promise in addressing the urgent medical needs of NMIBC patients.

Fast Track Designation is granted to investigational drugs intended for the treatment of serious conditions with unmet medical needs, facilitating their expedited development and review process. With FTD, Ractigen gains enhanced opportunities for collaboration with the FDA, enabling closer communication and expedited guidance throughout the development and regulatory review process.

Dr. Long-Cheng Li, Founder and CEO of Ractigen Therapeutics, expressed his enthusiasm about the FDA’s decision: "We are thrilled to receive Fast Track Designation for RAG-01, marking a significant milestone not only for our program but also for the saRNA field as a whole. This designation underscores the urgency and importance of advancing innovative therapies like RAG-01 to address critical medical needs. We remain dedicated to accelerating the development of innovative saRNA therapies to address a wide range of diseases, including cancer, genetic disorders, and chronic conditions. Through strategic collaborations and pioneering research efforts, the company aims to deliver transformative treatments that improve patient outcomes and quality of life."

About RAG-01: RAG-01 is a pioneering saRNA candidate engineered to target and activate the tumor suppressor gene p21 via the mechanism of RNAa. Traditionally considered "undruggable," p21 presents a unique opportunity for saRNA-based targeted activation. The drug, delivered through intravesical instillation using Ractigen’s proprietary LiCO delivery technology, has shown significant tumor suppression in mouse orthotopic bladder cancer models. Currently, the Phase I clinical trial of RAG-01 in Australia has successfully enrolled and dosed the first three patients. Its development marks a significant stride in RNAa based therapies, addressing the unmet needs of NMIBC patients.

About NMIBC: NMIBC represents 50-80% of all bladder cancer cases. Despite standard treatments like transurethral resection of bladder tumor (TURBT) followed by intravesical BCG or chemotherapy, recurrence rates remain high, estimated at 50-70% within the first five years. RAG-01’s development is a significant step towards addressing this substantial unmet need in bladder cancer therapy.

About RNAa: Pioneered by Dr. Long-Cheng Li and his team, RNAa is a clinically validated platform technology. It employs saRNA to target gene regulatory domains, activating gene expression and restoring therapeutic protein levels. This technology has vast potential for developing therapeutic drugs across various diseases, especially where traditional methods fall short, including cancer, genetic disorders, chronic diseases, and metabolic and cerebrovascular disorders.