Nanobiotix Announces Completion of Phase 1 Dose Escalation and NBTXR3 Recommended Phase 2 Dose for the Treatment of Inoperable, Recurrent Lung Cancer in Patients Amenable to Re-Irradiation

On April 2, 2024 NANOBIOTIX, a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported completion of the dose escalation part of a Phase 1 study evaluating potential first-in-class radioenhancer NBTXR3 for patients with non-small cell lung cancer ("NSCLC") that cannot be treated by surgery ("inoperable"), and has come back ("recurrent") (Press release, Nanobiotix, APR 2, 2024, View Source [SID1234641702]). whom have previously been treated with definitive radiation therapy and are amenable to re-irradiation. The Phase 1 study ("Study 2020-0123") is being conducted by The University of Texas MD Anderson Cancer Center ("MD Anderson") as part of an ongoing strategic collaboration with Nanobiotix.

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"NBTXR3 is designed as a product candidate with the potential to improve treatment outcomes for patients with cancer in any setting where radiotherapy is a part of the treatment regimen. While these patients experience different cancer types and are each faced with unique challenges, what they share is an urgent need for therapeutic innovation with the chance to make a difference," said Louis Kayitalire, MD, Chief Medical Officer at Nanobiotix. "We believe the injection feasibility and favorable safety profile we have observed from the completed dose escalation part of this Phase 1 lung cancer study could pave the way for additional clinical development of NBTXR3 for patients with inoperable, recurrent lung cancer and patients amenable to re-irradiation."

The completed dose escalation part of Study 2020-0123 established the recommended Phase 2 dose after determination of injection feasibility and observation of a favorable safety profile. The expansion part of the study, further evaluating safety and early signals of efficacy, is ongoing.

About MD ANDERSON STUDY 2020-0123
MD Anderson Study 2020-0123 (NCT04505267) is a Phase 1 study evaluating the best dose and observing the adverse effects of NBTXR3 activated by radiation therapy ("RT") for the treatment of non-small cell lung cancer ("NSCLC") that cannot be treated with surgery ("inoperable"), and has come back ("recurrent"), in patients who have previously been treated with definitive RT. The primary objectives of the study include a safety assessment of re-irradiation in these patients and determination of the recommended Phase 2 dose of NBTXR3 activated by RT. The re-irradiation safety assessment part and the dose-finding part of the study have completed. An expansion part evaluating additional signals of safety, feasibility, anti-tumor response, and time-to-event outcomes is ongoing.

About NBTXR3
NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles that is administered via one-time intratumoral injection and activated by radiotherapy. Its proof-of-concept was achieved in soft tissue sarcomas for which the product received a European CE mark in 2019. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

Radiotherapy-activated NBTXR3 is being evaluated across multiple solid tumor indications as a single agent or in combination with anti-PD-1 immune checkpoint inhibitors, including in NANORAY-312—a global, randomized phase III study in locally advanced head and neck squamous cell cancers. In February 2020, the United States Food and Drug Administration granted regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced HNSCC who are not eligible for platinum-based chemotherapy—the same population being evaluated in the phase III study.

Given the Company’s focus areas, and balanced against the scalable potential of NBTXR3, Nanobiotix has engaged in a collaboration strategy to expand development of the product candidate in parallel with its priority development pathways. Pursuant to this strategy, in 2019 Nanobiotix entered into a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to sponsor several phase I and phase II studies evaluating NBTXR3 across tumor types and therapeutic combinations. In 2023 Nanobiotix announced a license agreement for the global co-development and commercialization of NBTXR3 with Janssen Pharmaceutica NV, a Johnson & Johnson company.

Freenome Announces Topline Results for PREEMPT CRC® to Validate the First Version of its Blood-Based Test for the Early Detection of Colorectal Cancer

On April 2, 2024 Freenome, a biotechnology company pioneering an early cancer detection platform, reported topline results from PREEMPT CRC, a prospective, registrational clinical study to validate its blood-based test for the early detection of colorectal cancer (CRC) among average-risk adults (Press release, Freenome, APR 2, 2024, View Source [SID1234641718]).

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In a prespecified analysis, the Freenome blood test for CRC screening demonstrated 79.2% sensitivity in detecting colorectal cancer (Stage I: 57.1%, Stage II: 100%, Stage III: 82.4%, Stage IV: 100%) with 91.5% specificity for non-advanced colorectal neoplasia. The test also showed 12.5% sensitivity in detecting advanced adenomas (AA), with a sensitivity of 29% for AAs with high-grade dysplasia, also referred to as Stage 0. All endpoints were powered at 96% or greater.

When specificity was adjusted to the Centers for Medicare and Medicaid Services (CMS) National Coverage Determination (NCD) cut-off of 90%, there was a corresponding increase in the sensitivity for AA (14.8%) while maintaining CRC sensitivity. With the addition of proteins, an improved sensitivity for both AA (16.4%) and CRC (80.5%) at the 90% cut-off was observed. Additional study findings will be presented at a future scientific meeting.

"These results advance our early cancer detection programs toward mainstream clinical use, and we are grateful to the participants, partners and communities who helped accomplish this study," said Lance Baldo, M.D., chief medical officer at Freenome. "PREEMPT CRC was designed and executed with high scientific rigor and generated valuable data and insights that enable near- and long-term test improvements. These clinical performance metrics set a standard from which Freenome will continue to innovate, including the evaluation of prespecified test versioning."

PREEMPT CRC was a prospective, registrational study designed to validate the Freenome blood test for CRC screening. Conducted at more than 200 sites, the study enrolled 48,995 asymptomatic, average-risk adults between the ages of 45 and 85 scheduled to undergo a screening colonoscopy. The results were based on data from the 27,010 eligible participants who enrolled consecutively in the study after a predetermined cut-off date. The retained samples from these participants, along with samples from over 16,000 additional participants not utilized in the present analysis, remain available to support future test improvements.

The study leveraged a hybrid model involving virtual and traditional recruitment methods to reach underserved communities and ensure a representative population that includes people from all 48 states in the continental U.S. In addition, real-world data (RWD) collection through tokenization was integrated into the trial to complement the molecular data with longitudinal clinical outcomes that can be applied to CRC and other early cancer detection applications as part of the company’s platform and test versioning roadmap.

"While physicians have screening tools available for colorectal cancer, the associated inconvenience and discomfort of these methods deter many from getting recommended screenings," said Aasma Shaukat, M.D., M.P.H., professor of medicine at the NYU Grossman School of Medicine and a principal investigator for the PREEMPT CRC study. "By providing a more convenient option, Freenome’s blood test for the early detection of CRC has the potential to boost screening adherence rates and improve accessibility for people in all communities."

"In the PREEMPT CRC study, we brought communities together to confront a common enemy – cancer," said Mike Nolan, chief executive officer at Freenome. "We built Freenome to be able to integrate many analytes and computational methods into one test to implement a ‘staircase’ of increasing performance for the benefit of patient care. The performance of this initial version establishes a strong foundation and we expect to broaden it to other cancers. Our platform uniquely enables our team to efficiently iterate as we consistently push to achieve what is possible for patients."

About PREEMPT CRC
PREEMPT CRC (NCT04369053) was a prospective, registrational clinical study to validate Freenome’s blood test for the early detection of colorectal cancer (CRC) among average-risk adults. Initiated in 2020, the study was conducted at more than 200 sites and enrolled 48,995 asymptomatic, average-risk participants between the ages of 45 and 85 scheduled to undergo a screening colonoscopy. Freenome and the U.S. Food and Drug Administration agreed upon a predetermined cut-off date for the period most affected by the COVID-19 pandemic. Of the 48,995 participants enrolled, 27,010 were evaluated.

The study leveraged a novel hybrid model involving virtual and traditional recruitment methods to reach underserved communities and ensure a representative population. The decentralized recruitment strategy underscores Freenome’s commitment to promoting equity and diversity in clinical studies, ensuring its tests are designed for everyone.

Freenome’s partners in PREEMPT CRC included the Colorectal Cancer Alliance, Dia de la Mujer Latina, the Intercultural Center for Health Research and Wellness, and historically Black colleges and universities (HBCUs), including Morehouse School of Medicine. Freenome also worked with CVS Health Clinical Trial Services to help drive study enrollment through coordinated communication efforts targeting patients with already scheduled colonoscopies.

About Colorectal Cancer
Though colorectal cancer (CRC) is curable if detected early, sub-optimal screening rates mean CRC is often detected too late for successful treatment, making it the second cause of cancer deaths in the U.S.2 Nearly twice as many people under the age of 55 are diagnosed with CRC than a decade ago, and more people are dying from the disease each year.3 In response, the U.S. Preventive Services Task Force lowered the screening guidelines for average-risk adults from 50 to 45 years old.4

Following screening guidelines can improve detection rates, and catching CRC early can lead to better outcomes.4 Despite the effectiveness of screenings in reducing CRC mortality, only 59% of U.S. adults adhere to screening guidelines.5 Recent data show that providing a blood test as a screening option to individuals who previously declined a colonoscopy or stool test increased screening rates.

NeoVirTech obtains funding from the AAP France 2030 to develop innovative theranostic platform for cancer virotherapies

On April 2, 2024 NeoVirTech reported the company in partnership with Imactiv-3D, the ImPACT team from the Cancer Research Center of Toulouse and the National Veterinary School of Toulouse, obtains funding from AAP France 2030 organized by the French Government and the Occitanie region for the development of an innovative theranostic platform for cancer virotherapy, in strong collaboration with CHU de Toulouse and Oncopole Claudius Régaud (Press release, NeoVirTech, APR 2, 2024, View Source [SID1234641703]).

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This program, called Perseverance, supported by Transgene, aims to accelerate the preclinical development of oncolytic viruses (OV), viruses modified and armed to specifically destroy cancer cells. The program is organized into different work tasks, involving the design of ANCHORTM autofluorescent VO candidates for in vivo monitoring of infection and replication of VOs, their production and validation. ANCHOR VOs are then used to perform a virogram on different cancer cell lines to achieve precise mapping of oncolytic activities. The VOs are then optimized and tested for their interaction with pre-existing treatments. Finally, ANCHORTM VOs are tested on organoids derived from patients tumors, the infection of which is analyzed by deep learning and AI processes, and tested on animal models (mouse/rabbit).

At the end of the program, Perseverance offers a clear vision of the efficiency of a given VO on the most relevant models and close to the patient, in order to accelerate their development and guide clinical and therapeutic decisions.

The program is open to any VO of interest, regardless of their stage of development. For more information: [email protected]

Jazz Pharmaceuticals Completes Zanidatamab Biologics License Application for Previously Treated HER2-Positive Metastatic Biliary Tract Cancer

On April 2, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the company has completed the rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for the HER2-targeted bispecific antibody zanidatamab as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) (Press release, Jazz Pharmaceuticals, APR 2, 2024, View Source [SID1234641719]). If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S.

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"This important milestone brings us one step closer to delivering zanidatamab, a targeted treatment option, to patients living with HER2-positive BTC, a type of cancer that is associated with a five-year overall survival rate of less than 5%," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Zanidatamab is a biparatopic HER2-targeted bispecific antibody that simultaneously binds two non-overlapping epitopes of HER2 resulting in multiple mechanisms of action. Second-line (2L) BTC represents the first of multiple indications we are evaluating and we are excited about zanidatamab’s potential as a new option for multiple HER2-expressing cancers, with ongoing Phase 3 trials in 1L BTC, 1L gastroesophageal adenocarcinoma (GEA), and previously treated breast cancer."

The BLA includes data from the Phase 2b HERIZON-BTC-01 trial of zanidatamab in previously treated HER2-positive BTC. The primary endpoint was confirmed objective response rate (cORR) by independent central review (ICR) in Cohort 1. Data as of Oct. 10, 2022, from the 80 HER2-positive BTC patients enrolled in Cohort 1 of the trial demonstrated a cORR of 41.3% [95% confidence interval (CI): 30.4, 52.8] with a Kaplan Meier (KM) estimated median duration of response (DOR) of 12.9 months [95% CI: 6.0-not estimable] by ICR. Historical response rates for 2L standard-of-care chemotherapy in patients with BTC are reported to be 5 to 15%1,2. The KM estimated median progression-free survival (PFS) was 5.5 months [95% CI: 3.7, 7.2] with a range of 0.3 to 18.5 months.

Zanidatamab demonstrated a manageable and tolerable safety profile, with only two patients (2.3%) in HERIZON-BTC-01 experiencing adverse events (AEs) leading to treatment discontinuation. There were no Grade 4 AEs, and no deaths were considered treatment-related. The most common AEs were diarrhea and infusion-related reactions, which were predominately low-grade, reversible and manageable prophylactically with routine supportive care.

These data were featured as an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2023, published in The Lancet Oncology, and included in the 2023 Best of ASCO (Free ASCO Whitepaper) program. Quality-of-life data from this trial were also presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 and at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.

The HERIZON-BTC-302 Phase 3 trial (NCT06282575) of zanidatamab in 1L advanced or metastatic HER2-positive BTC was recently initiated and is open for enrollment. The global, open-label, randomized trial will evaluate the efficacy and safety of zanidatamab in combination with standard-of-care therapy against standard-of-care therapy alone. The primary objective of the study is to compare the efficacy of zanidatamab and chemotherapy (cisplatin plus gemcitabine) with or without the addition of a programmed death protein 1/ligand 1 (PD-1/L-1) inhibitor versus chemotherapy with or without a PD-1/L1 inhibitor in patients. HERIZON-BTC-302 is proposed as the confirmatory trial for zanidatamab in BTC.

About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design and increased binding results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Biliary Tract Cancer
Biliary tract cancer (BTC), including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers and are often associated with a poor prognosis3,4. The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with BTC annually5,6,7,8 and most patients (> 65%) are diagnosed with tumors that cannot be removed surgically.

Phio Pharmaceuticals Reports 2023 Year End Financial Results and Provides Business Update

On April 2, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology is designed to make immune cells more effective in killing tumor cells, reported its financial results for the year ended December 31, 2023 and provided a business update (Press release, Phio Pharmaceuticals, APR 2, 2024, View Source [SID1234641704]).

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Recent Corporate Updates

PH-762

In 2023, we made substantial progress as a focused drug development organization. In April, we submitted our first IND to the U.S. Food and Drug Administration (FDA), addressing an immuno-oncology disorder and seeking clearance to commence a Phase 1B dose escalation trial in various forms of skin cancer with our lead INTASYL compound PH-762. One month later we received clearance from the FDA to begin our trial in stage IV melanoma, Merkel cell and cutaneous squamous cell carcinoma (cSCC), including the early stages I and II in cSCC. The latter clearance was significant since there are no drugs specifically approved to treat early stages I and II of cSCC. The current standard of care for these diseases is surgical intervention, which may not always be an ideal medical option when tumor size or placement occur on certain areas of the face and scalp. Our INTASYL compound PH-762 may offer an alternative which could shrink tumor size, if not eliminate the lesion, as well as reducing the extent of surgical intervention to allow for tissue sparing and facilitating a faster patient recovery.

As of February, the first two patients in our first cohort have completed treatment with PH-762 with no reported adverse events.

We now have four investigation sites under contract to participate in the trial. The sites consist of George Washington University, Banner MD Anderson, Centricity and Integrity Research.

AgonOx Study Development

In February 2021, we entered into a clinical co-development collaboration agreement (the "Clinical Co-Development Agreement") with AgonOx, a private company developing a pipeline of novel immunotherapy drugs targeting key regulators of the immune response to cancer. Under the Clinical Co-Development Agreement, we and AgonOx are working to develop a T cell-based therapy using PH-762, and AgonOx’s "double positive" tumor infiltrating lymphocytes ("DP TIL") technology. AgonOx is conducting a Phase 1 clinical trial of PH-762 treated DP TIL in patients with advanced melanoma and other advanced solid tumors. In August and September, AgonOx infused the first two patients with their DP TIL. In November, a third patient was infused with a combination of TIL and our PH-762 product candidate. Further patient infusions have been delayed due to a facility renovation at the Providence Cancer Research Center, which is expected to reopen in May 2024.

Cost Rationalization

In 2023 we implemented a cost rationalization program driven by our transition from discovery research to product development. This resulted in a decision not to renew our building lease in Marlborough, MA., which lease expires on March 31, 2024. A smaller research footprint has been established in the Massachusetts Biomedical Initiatives in Worcester, MA, where we occupy 321 sq. ft of laboratory space. Additionally, we rationalized discovery research personnel resulting in a headcount reduction of 36%. Expense reductions have been redirected to funding the Phase 1B clinical trial of PH-762.

Patent Portfolio Enhancement

Two new patent applications were filed covering the intratumoral administration of PH-762 for the treatment of various skin cancers, and the synergistic combination of an INTASYL compound and a systemic antibody. In addition, five new patents covering multiple INTASYL compounds were granted in the US (2), Japan (1), South Korea (1) and Hong Kong (1).

Scientific News

We presented new data on the immunotherapeutic activity of INTASYL compounds alone and as Adoptive Cell Therapy at conferences, including American Academy of Cancer Research (AACR) (Free AACR Whitepaper), Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper), and at the triple meeting of AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). New data was presented on INTASYL PH-894 showing that local treatment with PH-894 presents a strategy to decrease BRD4 expression and upregulate MART-1 expression to increase immune response to cancer cells while reducing toxicities associated with systemic therapies. This further supports development of PH-894 for injectable solid tumor indications such as melanoma.

In addition, data was presented that demonstrates the effectiveness of PH-894 as an antitumor cytotoxic agent (directly killing tumor cells). The addition of PH-894 to cells in vitro elicited concentration-associated apoptosis of all human cancer cell lines tested, including head and neck squamous cell carcinoma (HNSCC), breast cancer, lung cancer, glioblastoma, melanoma, colon cancer, ovarian cancer, and cervical cancer.

As previously disclosed, we have elected to defer further work on our PH-894 product candidate in order to prioritize and advance our PH-762 clinical trials.

Financial Results

Cash Position

At December 31, 2023 we had cash of $8.5 million as compared with $11.8 million at December 31, 2022.

Research and Development Expenses

Research and development expenses were $6.3 million for the year ended December 31, 2023 as compared with $7.0 million for the year ended December 31, 2022, a decrease of 10%. The decrease was primarily due to decreased costs related to the completion of our IND-enabling preclinical studies for PH-894 and reduced lab supplies as a result of a decrease in lab personnel and a shift in focus on clinical development, partially offset by an increase in clinical-related costs for the two U.S. PH-762 Phase 1 clinical trials as compared to the prior year period.

General and Administrative Expenses

General and administrative expenses were $4.4 million for the year ended December 31, 2023 as compared with $4.5 million for the year ended December 31, 2022, a decrease of 2%. The decrease was primarily due to decreases in personnel-related expenses related to organizational department changes, one-time executive search-related fees for our President and CEO and D&O insurance premiums, partially offset by increased professional fees for legal services as compared to the prior year period.

Net Loss

Net loss was $10.8 million, or $5.20 per share, for the year ended December 31, 2023 as compared with $11.5 million, or $10.10 per share, for the year ended December 31, 2022. The decrease in net loss was primarily due to the changes in research and development expenses, as described above.