On October 26, 2020 NANOBIOTIX (Euronext : NANO – ISIN : FR0011341205 – the ‘‘Company’’) reported updates to the Company’s global development plan for first-in-class radioenhancer NBTXR3 at the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting (Press release, Nanobiotix, OCT 26, 2020, View Source [SID1234569064]).

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While the COVID-19 crisis and subsequent measures to curtail the spread of the virus have created challenges in clinical trial recruitment, a sharpened focus on the Company’s priority pathways in head and neck cancer and immunotherapy has led to the continued achievement of necessary milestones for the development of lead product candidate NBTXR3. Moreover, diligent efforts in collaboration with The University of Texas MD Anderson Cancer Center (MD Anderson) in the United States (US) has helped to advance expansion of the development plan across new indications.

Priority Development in Head and Neck Cancer and Immunotherapy

Pathway to Global Registration in Head and Neck Cancer On Track

Nanobiotix has presented an update on the expansion part of the Company’s phase I study evaluating NBTXR3 activated by radiation therapy for patients with head and neck cancer (Study 102) at ASTRO 2020. In 31 evaluable patients, positive results confirmed the target lesion objective response rate presented earlier this year at 83.9% and showed an increase in target lesion complete response rate at 67.7%. The target lesion complete response rate is an increase over previously reported data (60%) with additional follow up (7.8-month median follow up vs. 5 months). Additionally, data showed an overall objective response rate of 83.9% and an overall complete response rate of 48.4%, which were also increases over previously reported data (83% and 43% respectively).

The trial has recruited 44 patients in total (31 evaluable to date), and will remain ongoing until reaching 44 evaluable patients. The next update on the study is expected in the second quarter of 2021.

Preparation for the Company’s pivotal phase III trial evaluating NBTXR3 activated by radiation therapy for patients with head and neck cancer (NANORAY-312) is ongoing as planned. The trial is expected to commence after the financing to fund the trial is secured.

As previously announced, NBTXR3 activated by radiation therapy for the population in NANORAY-312 received Fast Track designation from the US Food and Drug Administration (FDA) in February 2020. Fast Track is a process designed to facilitate the development and accelerate the review of drugs for serious conditions and that have the potential to address unmet medical needs. The purpose is to expedite the availability of new treatment options for patients.

First Clinical Data in Immunotherapy to be Presented in Coming Weeks

Nanobiotix will present the first clinical results from a phase I study evaluating NBTXR3 activated by radiation therapy in combination with pembrolizumab or nivolumab for patients with head and neck cancer, lung metastasis and/or liver metastasis (Study 1100) by the end of 2020.

Nine patients have been injected in the trial thus far and recruitment remains ongoing. After the release of first results, the next step for the trial will be establishment of the recommended phase II dose (RP2D) by mid year 2021 for the head and neck cancer cohort and the lung metastasis cohort, and in the second half of 2021 for the liver metastasis cohort.

Early-Stage Development Across Other Solid Tumor Indications and with Collaborators

Nanobiotix Trials in Additional Solid Tumor Indications

The dose escalation part of the Company’s phase I/II trial evaluating NBTXR3 activated by radiation therapy for the treatment of patients with hepatocellular carcinoma (HCC) or liver metastasis (Study 103) has completed successfully and final data has been presented at ASTRO 2020. Data showed that the product candidate continues to be safe and well tolerated with no dose-limiting toxicities (DLTs). Early efficacy data showed a target lesion objective response rate of 90.9% in evaluable patients with hepatocellular carcinoma (HCC) and a target lesion objective response rate of 71.4% in evaluable patients with liver metastasis. Further development in this indication will proceed after the launch of the Company’s phase III head and neck cancer trial.

The Company’s phase I trial evaluating NBTXR3 activated by radiation therapy for the treatment of patients with prostate cancer (Study 104) has administered NBTXR3 to five patients, with no serious adverse events and no DLTs reported. At present the Company has paused development in this indication to focus resources on the head and neck cancer and immunotherapy pathways.

In soft tissue sarcoma, the final patient follow up visit has been completed in the phase III Act.In.Sarc study. The planned post-registrational trial is expected to launch in 2021.

Trials with Collaborators

The Company’s clinical collaboration with MD Anderson continues to move forward with the launch of a phase I trial evaluating NBTXR3 activated by radiation therapy for patients with pancreatic cancer. FDA ‘Safe to Proceed’ notifications have been received for four additional trials in the collaboration and are pending activation.

About NBTXR3

NBTXR3 is a first-in-class radioenhancer composed of functionalized hafnium oxide nanoparticles that is administered via one-time intra-tumoral injection and activated by radiation therapy. The physical and universal mode of action (MoA) of NBTXR3 is designed to trigger cellular destruction death and adaptive immune response.

NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) of the oral cavity or oropharynx in elderly patients unable to receive chemotherapy or cetuximab with limited therapeutic options. Promising results have been observed in the phase I trial regarding local control. In the United States, the Company has started the regulatory process to commence a phase III clinical trial in locally advanced head and neck cancers. In February 2020, the United States Food and Drug Administration granted the 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 head and neck squamous cell cancer who are not eligible for platinum-based chemotherapy.

Nanobiotix is also running an Immuno-Oncology development program. The Company has launched a Phase I clinical trial of NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors in locoregional recurrent (LRR) or recurrent and metastatic (R/M) HNSCC amenable to re-irradiation of the HN and lung or liver metastases (mets) from any primary cancer eligible for anti-PD-1 therapy.

Other ongoing NBTXR3 trials are treating patients with hepatocellular carcinoma (HCC) or liver metastases, locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and pancreatic cancer. The Company is also engaged in a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to further expand the NBTXR3 development program.

On October 26, 2020 Anpac Bio-Medical Science Co., Ltd. ("Anpac Bio," the "Company" or "we") (ANPC), a biotechnology company with operations in China and the United States focused on early cancer screening and detection, reported that it has completed over 200,000 cancer detection tests as of September 30, 2020 using its biophysics based cancer screening technology, Cancer Differentiation Analysis ("CDA") (Press release, Anpac Bio, OCT 26, 2020, View Source [SID1234569063]).The CDA technology allows cancer screening for close to 60 types of cancer, including certain cancer types such as esophageal cancer and brain tumors which do not yet have other more-established blood based testing methods.

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As of June 30, 2020, the Company completed an accumulated number of CDA-based tests to 180,673. Since then, Company has carried out over 20,000 additional tests by the end of September, bringing the total number of tests over 200,000.

Dr. Chris Yu, CEO and Chairman of Anpac Bio commented, "We are very pleased to have achieved this milestone of over 200,000 completed biophysics based CDA tests. The rapid increasing number of tests we have achieved indicates the viability and popularity of our products, and indicates that biophysics based cancer screening technology can be an effective alternative approach to traditional cancer screening methods due to its advantages in a number of critical areas, including the detection of multiple cancer types at earlier stages due to a high level of sensitivity and specificity and low cost approach."

On October 26, 2020 BioInvent International AB ("BioInvent") (OMXS: BINV), a biotech company focused on novel and first-in-class immune-modulatory antibodies for cancer immunotherapy,reported it has received regulatory authority approval of its clinical trial application (CTA) in Denmark for a Phase I/IIa, first-in-human study of BI-1808, as monotherapy and in combination with the anti-PD-1 therapy Keytruda (pembrolizumab) for the treatment of solid tumors and cutaneous T-cell lymphoma (CTCL) (Press release, BioInvent, OCT 26, 2020, View Source [SID1234569062]).

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Martin Welschof, CEO of BioInvent, says, "CTA approval for our Phase I/IIa trial of BI-1808 marks the first anti-TNFR2 antibody to enter clinical development. BI-1808 is a first-in-class anti-TNFR2 antibody, which we believe is a very promising approach for cancer therapy, and testament to the power of our proprietary n-CoDeR and F.I.R.S.TTM platforms to generate antibodies to novel targets with potent anti-tumoral activity. We expect to enroll the first patient before the end of the year and to submit an investigational new drug (IND) application in the U.S. in the coming weeks."

The study will explore the safety, tolerability, and potential signs of efficacy of BI-1808 as a single agent and in combination with Keytruda in patients with ovarian cancer, non-small cell lung cancer and CTCL. It will also investigate the expression of potential immunological markers that might be associated with clinical responses. The trial will be conducted at several sites across Europe and the U.S. and is expected to enroll approximately 120 patients.

The Phase I stage is divided into two parts. Part A is a dose escalation of BI-1808 to assess safety, tolerability, pharmacokinetics/pharmacodynamics, and to determine the recommended dose as a single agent for Phase II trials. It will be followed by part B, which will explore the safety, tolerability and recommended dose of BI-1808 in combination with Keytruda. The Phase IIa will consist of expansion cohorts to assess signs of efficacy of BI-1808 as single agent and in combination with Keytruda in lung cancer and ovarian cancer patients. A separate cohort will explore the activity as single agent in CTCL (Sézary syndrome and mycosis fungoides).

On October 26, 2020 Cyclacel Pharmaceuticals, Inc. (Nasdaq: CYCC) (Nasdaq: CYCCP) (Cyclacel or the Company), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported clinical data demonstrating safety, anti-tumor activity and good oral bioavailability of Cyclacel’s CDK2/9 inhibitor fadraciclib in patients with advanced solid tumors (Press release, Cyclacel, OCT 26, 2020, View Source [SID1234569060]). The data were presented at an oral presentation at the Plenary Session of the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2020 held virtually on October 24-25, 2020.

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"In addition to good oral bioavailability, we are pleased to report a durable PR with continuing shrinkage of target lesions reaching 92% in a patient with MCL1 amplified endometrial cancer. Four other patients achieved stable disease," said Spiro Rombotis, Chief Executive Officer of Cyclacel. "The data support clinical development of fadraciclib in our planned Phase 1b/2a study in advanced endometrial and ovarian cancer and CDK4/6 inhibitor resistant breast cancer. Along with safety and efficacy the study will evaluate cyclin E, MCL1 and/or MYC biomarkers which are relevant to fadraciclib’s mechanism of action. In addition to our studies in solid tumors we are encouraged by evidence of antileukemic activity in our studies of fadraciclib in hematological malignancies. We are looking forward to reporting updated data from ongoing studies of fadraciclib and CYC140, our selective PLK1 inhibitor."

Presentation Highlights: Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of Fadraciclib (CYC065), a Cyclin-Dependent Kinase Inhibitor, in Patients with Advanced Cancers

Twenty-four heavily pretreated patients with various advanced solid tumors, including ovarian, endometrial/uterine, breast, and fallopian cancer, were enrolled in part 2 with intravenous (i.v.) administration and five patients in part 3 with oral administration of this ongoing Phase 1, open label, dose escalation study.

Primary Objective:

Determine MTD and recommended phase 2 dose (RP2D)
Secondary Objectives:

Evaluate pharmacokinetics
Assess pharmacodynamic markers
Design:

Administration schedule of flat dosing schedule of single-agent fadraciclib (CYC065) given either by 1-hour infusion or orally on days 1, 2, 8 and 9 every 3 weeks
Safety:

The trial advanced through four dose levels (DL) with a range of 90mg to 213mg, administered as a 1-hour intravenous infusion on days 1, 2, 8 and 9 and two DL with a range of 75mg to 150mg as an orally administered formulation on days 1, 2, 8 and 9; both in 3-week cycles.
Eleven patients were treated at DL4 (213 mg). Dose limiting toxicity at DL4 was reversible neutropenia. The 160mg dose level is being expanded to define RP2D.
No major or unexpected toxicities were observed.
Efficacy (n=24, i.v. formulation only):

One confirmed partial response and two stable disease (SD) out of 11 patients on 213mg i.v. formulation:
• PR after a month and a half on fadraciclib: MCL1-amplified endometrial cancer; failed seven lines of prior therapy; continuing treatment for more than 16 months with 92% reduction in target tumor lesions.
• SD: Cyclin E amplified ovarian cancer with 29% tumor shrinkage after four months.
• SD: Fallopian tube adenocarcinoma (undetermined protein level).
Pharmacokinetics (PK):

Increases in fadraciclib exposure with increasing dosing levels.
High oral bioavailability and comparable PK profile after oral or 1 hour-infusion administration.
The presentation was part of the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium 2020 and is available on the "Presentation and Events" section of the Cyclacel website at View Source

Presentation Details:

Title: Phase 1 safety, pharmacokinetic and pharmacodynamic study of fadraciclib (CYC065), a cyclin dependent kinase inhibitor, in patients with advanced cancers (NCT02552953)
Session Title: Late Breaking and Best Proffered Papers
Session Date and Time: Saturday 24 October 15:05 CET
Presentation Number: ORAL-002

About Cyclin-Dependent Kinases and Fadraciclib

Cyclin-dependent kinases (CDKs) are critical for cell cycle regulation and transcriptional elongation. Dysregulated CDKs have been linked to the cancer hallmarks of uncontrolled proliferation and increased survival. Fadraciclib is a potent orally and intravenously available inhibitor of CDK2 and CDK9.

Fadraciclib is in an ongoing Phase 1, first-in-human study in patients with advanced solid tumors. In part 1 of the study, target engagement and durable suppression of the MCL1 biomarker were observed after a single dose of fadraciclib by 4-hour infusion. Tumor shrinkage and stable disease were observed in five patients with cyclin E, MCL1 or MYC amplified advanced cancers treated at the RP2D. In the ongoing part 2 of the study evaluating a more intensive dosing regimen, a heavily pretreated patient with MCL1 amplified endometrial cancer achieved a radiographically confirmed partial response (PR) after a month and a half on fadraciclib. This patient continues on therapy for more than a year and reduction in her target tumor lesions has reached 92%. An additional patient with cyclin E amplified ovarian cancer achieved stable disease with 29% tumor shrinkage. Part 3 is investigating an oral dose formulation.

Fadraciclib is also being evaluated in Phase 1 combination studies with venetoclax in relapsed or refractory CLL and in relapsed or refractory AML or MDS. Similarly to FDA-approved CDK4/6 inhibitors, fadraciclib may be most useful in combination with other anticancer drugs, including BCL2 inhibitors, such as venetoclax, or HER2 inhibitors, such as trastuzumab. Preclinical data suggest that fadraciclib may benefit patients with adult and pediatric hematological malignancies such as CLL, AML, ALL, B-cell lymphomas, multiple myeloma and certain cyclin E-addicted or MYC-amplified solid tumors, including certain forms of breast cancer, neuroblastoma, ovarian cancer and uterine serous carcinoma.

On October 26, 2020 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported that the U.S. Food and Drug Administration (FDA) granted TRC102 orphan drug designation for the treatment of patients with malignant glioma, including glioblastoma (GBM) (Press release, Tracon Pharmaceuticals, OCT 26, 2020, View Source [SID1234569058]). TRC102 is a small molecule inhibitor of the DNA base excision repair pathway.

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TRC102 is being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA). TRC102 was evaluated in a Phase 2 trial in combination with Temodar chemotherapy in 19 patients with progressive or recurrent GBM who progressed following Temodar and external beam radiotherapy. Extended survival was observed in two patients for more than two years, both of whom demonstrated activation of the DNA base excision repair pathway and demonstrated hyperactivation of DNA damage response genes. TRC102 was also evaluated in combination with chemotherapy and external beam radiotherapy in a separate Phase 1 study of 15 patients with newly diagnosed non-squamous cell non-small cell lung cancer that resulted in a response by the Radiographic Evaluation Criteria in Solid Tumors (RECIST) in all patients, including three patients who had a complete response to treatment.

"Orphan drug designation for TRC102 underscores the high level of unmet medical need in patients with malignant glioma and supports its potential in this indication based on the previously reported data demonstrating prolonged survival in patients retreated with Temodar combined with TRC102," said James Freddo, M.D, Chief Medical Officer of TRACON. "We remain committed to developing TRC102 in collaboration with the National Cancer Institute and believe that the data generated to date provide a rationale to study TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma."

The FDA’s Orphan Drug Designation program provides orphan status to drugs and biologics that are being developed to address rare diseases or disorders that affect fewer than 200,000 people in the U.S. With orphan designation, TRACON qualifies for various incentives with respect to TRC102 for the treatment of glioblastoma, including tax credits for qualified clinical trials and seven years of market exclusivity upon receipt of regulatory approval.

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA). For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials.php.

About Malignant Glioma and GBM

GBM (also called glioblastoma) is a fast-growing malignant glioma that develops from star-shaped glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly spreading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults (12,630 men and 10,280 women) are diagnosed with brain and other nervous system cancer annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.