On October 2, 2024 Recursion, a leading clinical stage TechBio company decoding biology to industrialize drug discovery, reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for a Phase 1/2 clinical trial of REC-1245, a new chemical entity for the treatment of biomarker-enriched solid tumors and lymphoma (Press release, Recursion Pharmaceuticals, OCT 2, 2024, View Source [SID1234647003]).

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Chris Gibson, Ph.D., Co-founder and CEO of Recursion said, "REC-1245 is a prime example of using an expansive AI-enabled platform for drug discovery. After exploring many predicted biological and chemical relationships across our maps of biology, we identified RMB39 as a novel target that looks functionally similar to the well-known but hard to drug target CDK12. We also identified and optimized small molecules that target RBM39 without directly impacting CDK12 or CDK13 using these same AI-enabled maps. In under 18 months, leveraging some of our newer chemistry tools, Recursion rapidly progressed REC-1245 from novel target biology to preclinical drug candidate, more than twice the speed of industry average."

Recursion identified the novel regulatory role of RBM39 associated with CDK12 using its maps of biology and first reported this relationship in early 2023 at Download Day, Recursion’s R&D and investor event. Recursion believes the modulation of RBM39 may be associated with a therapeutic effect in certain biomarker-enriched solid tumors and lymphoma. Additionally, Recursion estimates that the initially addressable population for this potential therapeutic to be >100,000 patients in the US and EU5. REC-1245 is a potent and selective RBM39 degrader with a potential first-in-class profile. Preclinical data support that RBM39 degradation induces splicing defects which downregulate DNA Damage Response (DDR) networks and cell cycle checkpoints.

"RBM39 degraders may offer a promising therapeutic approach for patients with solid tumors, particularly those with limited treatment options," said Najat Khan, Ph.D., Chief R&D Officer and Chief Commercial Officer at Recursion. "Recursion’s platform was among the first to rapidly uncover the therapeutic potential of RBM39 degradation, a finding now validated by independent research. This mechanism provides new opportunities for targeting tumors, which are often resistant to conventional treatments. By advancing this research, we aim to deliver a critical option for patients facing significant unmet needs, ultimately improving their prognosis and quality of life."

The Phase 1/2 clinical trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and potential monotherapy efficacy of REC-1245, and is expected to initiate in Q4 2024.

On October 2, 2024 Processa Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing the next generation of chemotherapeutic drugs with improved efficacy and safety, reported that the first patient has been dosed in a Phase 2 clinical trial evaluating NGC-Cap for the treatment of advanced or metastatic breast cancer (Press release, Processa Pharmaceuticals, OCT 2, 2024, View Source [SID1234647002]).

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"Dosing the first patient in this Phase 2 trial is a significant step in the development of NGC-Cap as a more effective and better tolerated treatment than widely used capecitabine and 5-FU," stated David Young, PharmD, Ph.D., President of Research and Development at Processa. "We expect this Phase 2 trial to build upon NGC-Cap’s positive Phase 1b findings and we look forward to announcing the results from our interim analysis of this Phase 2 trial in mid-2025."

The Phase 2 trial (NCT06568692) is a global multicenter, open-label, adaptive designed safety-efficacy trial comparing two different doses of NGC-Cap to FDA-approved monotherapy capecitabine in approximately 60 to 90 patients with advanced or metastatic breast cancer. The trial is designed to evaluate the safety-efficacy profile of NGC-Cap versus monotherapy capecitabine, to determine the potential optimal dosage regimens of NGC-Cap as required by the FDA Project Optimus Initiative and to evaluate the possibility of personalizing NGC-Cap therapy.

To date, three clinical trial sites, including some with multiple clinical locations, have received institutional review board approval to participate in this study and are recruiting patients. Processa plans to activate approximately 30 sites worldwide.

Breast cancer is the second most common cancer and a leading cause of cancer-related death. More than 2 million cases of breast cancer were diagnosed in 2022 with more than 665,000 deaths globally. The five-year survival rate for those diagnosed with metastatic breast cancer is approximately 30%.

About Capecitabine Administered with PCS6422 (NGC-Cap)
NGC-Cap combines the administration of PCS6422, the Company’s irreversible dihydropyrimidine dehydrogenase (DPD) enzyme inhibitor, with low doses of capecitabine. Capecitabine is the oral prodrug of 5-fluorouracil (5-FU), and along with 5-FU is among the most widely used chemotherapy drugs, particularly for the treatment of solid tumors. When metabolized (after oral ingestion) it becomes 5-FU in the body, which, in turn, metabolizes to molecules called anabolites that actively kill duplicating cells, such as cancer cells, and to molecules called catabolites that only cause side effects. The presence of the DPD enzyme plays an integral role in the undesirable conversion of 5-FU to catabolites causing side effects while simultaneously decreasing tumor exposure to 5-FU and its cancer-killing anabolites.

On October 2, 2024 PDS Biotechnology, a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers and the development of infectious disease vaccines, reported that updated data from the IMMUNOCERV Phase 2 clinical trial evaluating Versamune HPV (formerly PDS0101) with chemoradiation to treat locally advanced cervical cancer were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2024 in an oral presentation by Adam Grippin, M.D., Ph.D., of The University of Texas MD Anderson Cancer Center (PubMed, PDS Biotechnology, OCT 2, 2024, View Sourcesec.gov/Archives/edgar/data/1472091/000114036124042537/ef20036539_ex99-1.htm" target="_blank" title="View Sourcesec.gov/Archives/edgar/data/1472091/000114036124042537/ef20036539_ex99-1.htm" rel="nofollow">View Source [SID1234647001]). The abstract was granted Basic/Translational Science Award from the ASTRO Annual Meeting Steering Committee.

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"HPV is responsible for virtually all cervical cancers and presents an opportunity for immunologic targeting1. However, there are currently no FDA-approved HPV-targeted immunotherapies to treat cervical cancer," said Ann Klopp, M.D., Ph.D., Professor of Radiation Oncology and Head of the Gynecologic Section at MD Anderson. "These data suggest that further investigation is warranted into the safety and efficacy of Versamune HPV in combination with standard of care in the treatment of locally advanced cervical cancer."

The IMMUNOCERV Phase 2 clinical trial (NCT04580771) evaluated the efficacy, safety and tolerability of Versamune HPV in combination with standard-of-care chemoradiotherapy for the treatment of locally advanced cervical cancer. The investigator-initiated study enrolled 17 newly diagnosed high-risk patients with large tumors of at least 5 cm in size. Highlights from the presentation include:

•All patients received at least 2 doses of Versamune HPV

•Median follow-up was 19 months

•36-month overall survival (OS) rate was 84.4%, and 100% for the eight patients who received all five doses of Versamune HPV. Historical published data show 36-month OS rate with chemoradiation in this population of approximately 64%.2

•36-month progression free survival (PFS) rate was 74.9%, among all patients and 100% for the eight patients who received all five doses of Versamune HPV. Historical published data show 36-month PFS rate with chemoradiation in this population of approximately 61%.2

•Complete metabolic response (CMR) was achieved in 15/17 (88%) patients

•Versamune HPV appeared to be safe and well-tolerated. The most common treatment-related toxicities were injection site reactions in twelve patients (71%).

"We are pleased that data from the Phase 2 IMMUNOCERV trial demonstrate compelling clinical activity and a promising safety profile," said Frank Bedu-Addo, Ph.D., President and Chief Executive Officer of PDS Biotech. "Based on our continued research in various HPV-positive cancers, Versamune HPV appears to work in combination with a variety of therapeutic agents to generate clinical responses and promote improved survival in patients with minimal toxicity. We look forward to the next steps in the development of Versamune HPV for locally advanced cervical cancer."

1. National Cancer Institute, Cervical Cancer Causes, Risk Factors and Prevention. View Source View Sourcecancer.gov/types/cervical/causes-risk-prevention

2. Rose PG, et al. Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer. N Engl J Med. 1999;340:1144-53.

On October 2, 2024 Kineta, Inc., a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that TuHURA Biosciences Inc (TuHURA) is exercising its right to extend their exclusivity and right of first offer agreement (the "Agreement") for Kineta’s VISTA blocking antibody KVA12123 (Press release, Kineta, OCT 2, 2024, View Source;utm_medium=rss&utm_campaign=kineta-announces-the-extension-of-the-tuhura-biosciences-exclusivity-and-right-of-first-offer-agreement-for-kva12123-kinetas-vista-blocking-antibody-currently-in-phase-1 [SID1234647000]). Under the terms of the Agreement entered in July 2024 between Kineta and TuHURA, TuHURA has the right to extend their rights for up to two 10-day periods. Kineta is entitled to receive $150,000 for each 10-day extension.

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"In February, Kineta announced that it would be exploring strategic alternatives for the company to maximize shareholder value. This priority continues, and I look forward to providing additional information on this front later this year," said Craig W. Philips, President, Kineta. "Through the exclusivity and right of first offer agreement with TuHURA for KVA12123, we reopened the Phase 1 clinical study in August 2024 and are currently enrolling patients into this study in advanced solid tumor cancers. Kineta is focused on completing the enrollment of the Phase 1 trial by year end 2024."

"KVA12123 is a novel, differentiated new treatment alternative for patients with cancer. The progress being made in the clinical trial is encouraging. As TuHURA continues our diligence, I have been pleased with the enthusiasm for KVA12123 that I have seen in the medical community. VISTA expression is broadly observed in patients with a number of solid and hematologic cancers. KVA12123 may provide a valuable therapeutic alternative to improving the treatment of patients with cancer," said Dr. James A. Bianco, Chief Executive Officer of TuHURA.

On July 8, 2024, Kineta announced that it had entered into the Agreement with TuHURA, a Phase 3 registration-stage immuno-oncology company developing novel technologies to overcome resistance to cancer immunotherapy. As part of the Agreement, Kineta received a $5 million nonrefundable payment from TuHURA in July 2024. Under the terms of the Agreement, any payment made by TuHURA in consideration for Kineta’s compliance with its obligations set forth in the Agreement will be credited to the upfront payment from TuHURA if a transaction between the parties is completed. In August, Kineta announced that in collaboration with TuHURA, it reopened enrollment in the VISTA-101 clinical trial. Kineta and TuHURA continue to collaborate on the ongoing Phase 1 clinical program for patients with advanced solid tumor cancer.

KVA12123, through the combination of unique epitope binding and an optimized IgG1 Fc region, has demonstrated strong tumor growth inhibition as both a monotherapy or in combination with other checkpoint inhibitors in preclinical models. KVA12123 provides a novel approach to address immune suppression in the TME with a mechanism of action that is differentiated and complementary with T cell focused therapies. KVA12123 may be an effective immunotherapy for many types of cancer including non-small cell lung (NSCLC), colorectal, renal cell carcinoma, head and neck, and ovarian cancer. Significant VISTA expression is observed in patients with a variety of cancer types including gynecologic tumors such as ovarian, cervical, and endometrial cancer.

On October 2, 2024 Kazia Therapeutics Limited (NASDAQ: KZIA), an oncology-focused drug development company, reported the presentation of data from a Phase I study (NCT04192981) evaluating concurrent paxalisib and radiation therapy (RT) in patients for the treatment of solid tumor brain metastases (BM) or leptomeningeal metastases (LM) harboring PI3K pathway mutations at the American Society for Radiation Oncology 66th Annual Meeting (ASTRO 2024), which is taking place from September 29 – October 2, 2024, in Washington, D.C (Press release, Kazia Therapeutics, OCT 2, 2024, View Source [SID1234646999]).

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"The encouraging response rates observed from this Phase 1 study suggests that the concurrent administration of the investigational brain penetrant PI3K inhibitor, paxalisib, in combination radiation therapy appears to be a viable treatment approach for addressing the tumor radioresistance in patients harboring PI3K pathway mutations," said John Friend, M.D., Chief Executive Officer of Kazia Therapeutics. "Additional data, including circulating tumor DNA (ctDNA) from this study will be presented at an upcoming 2024 scientific congress and discussions for a potential pivotal registration study to evaluate this unique combination therapy for patients with PI3K mutant brain metastases are ongoing."

Presentation details:

Title:    Multi-Center Phase I Study of Concurrent Paxalisib and Radiation Therapy in Patients with Solid Tumor Brain Metastases (BM) or Leptomeningeal Metastases (LM) Harboring PI3K Pathway Mutations
Presenter: Brandon S. Imber, M.D., M.A., Memorial Sloan Kettering Cancer Center
Abstract 1094
Scientific Session Title: CNS 4: Brain Mets and LMD
Session Date/Time: October 1, 5:15-6:15 PM ET
Summary Results from Part II of Phase 1 Study

•
Concurrent daily administration of paxalisib with brain radiotherapy was generally well-tolerated at a maximum dose of 45 mg per day in advanced solid tumor patients with brain metastases and PI3K pathway mutations;

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The most commonly reported adverse events in the study were nausea, vomiting and hyperglycemia;

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Established proof-of-principle for molecularly-selected, rational combination studies in radiation oncology to assess safety and ultimately efficacy;

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Treatment with 45mg paxalisib and radiotherapy demonstrated a 67% PR; and

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Over two-thirds of the patients at MTD achieved intracranial response which compares favorably to historical response rates for WBRT alone.

The Phase 1 study (n=17 evaluable) was a two-part, investigator-initiated trial evaluating the use of paxalisib with radiation therapy for the treatment of patients with PI3K pathway mutation brain metastases from solid tumors. Part I of the study established the MTD of paxalisib in combination with radiation therapy, while also demonstrating promising signs of clinical activity in all nine evaluable patients. Part II was a follow-on expansion cohort to further evaluate safety and efficacy of the MTD (45mg daily) combined with radiation therapy in up to 12 additional patients.

Approximately 200,000 cancer patients develop brain metastases in the United States each year. Radiotherapy is the mainstay of treatment for brain metastases, and generally consists of either stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) or some combination thereof. The efficacy in patients who receive WBRT differs according to the type of tumor and the number and volume of brain metastases, but several recent publications cite overall response rates of 20-45%. The increasing incidence of brain metastasis and the low response rates to existing treatments underscores the need for new treatment options.