On October 13, 2020 Kyowa Kirin International PLC (Kyowa Kirin), a wholly owned subsidiary of Kyowa Kirin Co., Ltd., reported data from a post hoc analysis of the MAVORIC trial. The analysis compared the efficacy and safety of POTELIGEO▼ (mogamulizumab) with vorinostat by patient blood classification in adult patients with mycosis fungoides (MF) and Sézary syndrome (SS), two types of CTCL.1 The data showed that higher levels of blood tumour involvement were associated with better patient outcomes in patients treated with mogamulizumab, compared to vorinostat.1

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MF and SS are subtypes of CTCL, a rare type of non-Hodgkin’s lymphoma that can affect the skin, blood, lymph nodes and internal organs.2 In MAVORIC, overall investigator-assessed progression-free survival (PFS) was significantly greater for patients treated with mogamulizumab compared to vorinostat, at 7.7 months and 3.1 months, respectively (P<0.0001).1 When data were stratified by blood classification, PFS was found to be significantly greater for mogamulizumab compared to vorinostat in patients with higher levels of blood involvement, known as B1 and B2 blood classifications.1

Professor Julia Scarisbrick, Consultant Dermatologist, lead author of this analysis from the study said: "In MF and SS, assessing the stage of the disease is key to prognosis, appropriate treatment and patient outcome. Assessment of blood involvement is part of this staging process. The data highlights that mogamulizumab is more effective in MF and SS patients who have blood involvement as part of their disease. Blood involvement is relatively common in the more advanced stages of CTCL and may be present in as many as 20% of less advanced cases.3 This new information could help improve the clinical management of MF and SS patients and highlights the need for blood monitoring."

Overall response rate (ORR) was also significantly greater for mogamulizumab than vorinostat in the MAVORIC trial at 28% and 5% respectively (P<0.0001).1 In this analysis, ORR was also found to be significantly greater for mogamulizumab than vorinostat in patients with B2 blood classification.1 Difference in ORR for patients with B1 blood classification was not significant between the two treatment groups.1 Difference in time-to-next-treatment (TTNT) was not significant for patients without blood involvement (B0 classification), but was significantly greater for mogamulizumab in patients with B1 or B2 blood involvement, 13.70 vs 3.30 months for mogamulizumab and vorinostat, respectively (P<0.0001).1 Drug-related treatment-emergent adverse events (TEAEs) were similar in patients regardless of blood involvement and were lower for mogamulizumab than vorinostat at each blood classification level.1

Danie du Plessis, Executive Vice President, Medical Affairs (EMEA) at Kyowa Kirin, commented: "We welcome the results of this analysis in furthering our understanding of the role of mogamulizumab in treating MF and SS patients. Research suggests that patients with B1 and B2 blood classifications may have reductions in median survival and an increased risk of disease progression, compared to those classified as B0.4 Through our work with this therapy, we are aiming to address the unmet needs in these patient populations and are dedicated to improving outcomes for people with MF and SS."

The data will be presented today in a poster session at the 16th European Association of Dermato Oncology (EADO) Congress.1

About Mycosis Fungoides (MF) and Sézary syndrome (SS)
MF and SS are subtypes of cutaneous T-cell lymphoma (CTCL), a rare type of non-Hodgkin’s lymphoma that can affect the skin, blood, lymph nodes and internal organs.2 CTCL is rare. For every 100,000 people in Europe, there are approximately 24 cases of CTCL.5 Together they represent approximately 65% of all cases of CTCL.2 Individuals with this disease often suffer from disfiguring, itchy, painful and unpredictable skin symptoms, which can lead to further complications that can impact their life expectancy.6,7

MF and SS are characterised by localisation of cancerous white blood cells called T lymphocytes (T cells), to the skin.8,9 These cancerous T cells consistently express a protein called CC-chemokine receptor 4 (CCR4), which enables them to move from the blood to the skin.10,11,12 When these cancerous T cells move to the skin, they can create a localised inflammatory immune skin response, commonly resulting in visible skin symptoms of red patches or plaques, 10,13,14,15,16 which can resemble psoriasis or eczema.8

MF and SS can affect the skin, blood, lymph nodes (part of the body’s immune system which is spread throughout the body) and internal organs.2 All four areas of the body are used to assess disease stage17,18 and clinically significant involvement of the blood, particularly in more advanced disease, is linked with increased morbidity and an overall reduction in patient survival.17,19,20

Due to its likeness to more common skin conditions such as eczema and psoriasis,8 CTCL can take, on average, between 2 and 7 years for individuals to receive a confirmed diagnosis.21 It is critical for doctors to diagnose CTCL as early as possible as the patient’s prognosis can be affected if the disease progresses to later stages.4 Whilst most individuals that present with early stage do not progress to a more advanced stage,22 patients with advanced disease have significantly poorer outcomes with only around half of patients (52%) surviving for just 5 years.17

About POTELIGEO (mogamulizumab)
POTELIGEO is a first-in-class humanised monoclonal antibody (mAb), designed to bind to CC chemokine receptor 4 (CCR4).7 After POTELIGEO binds to CCR4, it increases affinity of immune cells from the immune system to target the cancerous cells.23 POTELIGEO uses Kyowa Kirin’s proprietary POTELLIGENT technology.23

Following a positive opinion from Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), the European Commission (EC) granted marketing authorisation for POTELIGEO in November 2018 for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy.24 The CHMP’s opinion was based on results of the MAVORIC trial, the largest randomised study of systemic therapy in MF and SS,7 and the first trial to compare systemic therapies using progression-free survival as a primary endpoint.7

About the MAVORIC Trial

The MAVORIC trial is the largest randomised study of systemic therapy conducted in MF and SS,7 and the first trial to compare systemic therapies using ‘progression-free survival’ (PFS) as a primary endpoint, which incorporates looking at disease progression in four different compartments of the body (skin, blood, lymph nodes and internal organs).7
Secondary endpoints were overall response rate; duration of response (time from first achievement of an overall response to progression or death); the proportion of patients with an overall response in the crossover portion of the trial; assessment of quality of life; immunogenicity (immune response) and safety.7
Results showed that:
In patients taking POTELIGEO disease was controlled for more than twice as long as in those taking the comparator treatment, vorinostat* (PFS of 7.7 mths vs 3.1 mths) (HR=0.53, 95% CI: 0.41–0.69; p<0.0001).7
Overall significantly more patients responded to POTELIGEO than vorinostat* (Overall Response Rate [ORR] 28% versus 5%; Risk Ratio [RR]: 23.1; 95% CI 12.8–33.1, P<0.0001).7
Response to treatment lasted 43% longer in people taking POTELIGEO versus those taking vorinostat* (14.1 months versus 9.1 months).7
More patients responded to POTELIGEO, across all studied MF/SS disease stages than with vorinostat.* 7
POTELIGEO has overall good tolerability with a manageable safety profile.7,25
The most common adverse reactions with POTELIGEO are constipation, diarrhoea, nausea, stomatitis, fatigue, oedema (peripheral), pyrexia, infections, infusion related reactions, headache and drug eruption (including skin rash).24
——————————————————————————————-
*Vorinostat is a USA FDA-licensed existing treatment for MF and SS and is currently unlicensed in the EU

On October 13, 2020 NANOBIOTIX (Paris:NANO) (Euronext: NANO – ISIN: FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported that the first patient has been injected in its phase I study evaluating NBTXR3 activated by radiation therapy for patients with pancreatic cancer (Press release, Nanobiotix, OCT 13, 2020, View Source [SID1234568409]). The trial is a being conducted at The University of Texas MD Anderson Cancer Center (MD Anderson) as part of an ongoing clinical collaboration.

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Two additional trials from the clinical collaboration received ‘safe to proceed’ notifications from the United States Food and Drug Administration (FDA): (i) a phase I study evaluating NBTXR3 activated by radiation therapy for patients with lung cancer amenable to re-irradiation; and (ii) a phase I study evaluating NBTXR3 activated by radiation therapy with concurrent chemotherapy for patients with esophageal cancer. All current and future trials in this clinical collaboration are sponsored and executed by MD Anderson.

A Phase I Study Evaluating NBTXR3 Activated by Radiation Therapy in Patients with Pancreatic Cancer

Pancreatic cancer is a rare, deadly disease that accounts for approximately 3% of all cancers and has a 5-year survival rate of 9%1.

This pancreatic cancer trial is an open-label, single-arm, prospective phase I study consisting of two parts: (i) dose-escalation to determine the recommended phase 2 dose (RP2D) of NBTXR3 activated by radiation therapy; and (ii) expansion at RP2D.

The patient population will include adults (age ≥ 18 years) with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) that are radiographically non-metastatic at screening, and that have not previously received radiation therapy or surgery for pancreatic cancer. Up to 24 subjects will be enrolled and the planned enrollment period is 18 months.

The objectives of the study are the determination of dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), and the RP2D.

Two Additional Phase I Studies in Lung and Esophageal Cancer Pending

A phase I trial investigating NBTXR3 activated by radiation therapy for patients with lung cancer amenable to re-irradiation, and a phase I trial investigating NBTXR3 activated by radiation therapy with concurrent chemotherapy for patients with esophageal cancer have been deemed ‘safe to proceed’ by FDA. ‘Safe to proceed’ notifications are delivered once the agency is satisfied with the information contained in an investigational new drug application (IND) or any additional information or clarification has been provided.

Lung cancer is the second most common cancer type, and the leading cause of cancer death for both men and women. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with a 5-year survival rate of 24% worldwide.2

The lung cancer trial is an open-label, two-cohort, prospective phase I study consisting of two parts: (i) a radiation therapy safety lead-in, and NBTXR3 activated by radiation therapy dose-finding to determine the RP2D; and (ii) expansion at the RP2D with toxicity monitoring.

The patient population will include adults (age ≥ 18 years) with inoperable, locoregional recurrent (LRR) non-small cell lung cancer (NSCLC) stage IA to IIIC that are radiographically non-metastatic at screening and have previously received definitive radiation therapy. Cohort 1 will evaluate the safety of intensity-modulated radiation therapy (IMRT) monotherapy in 10 patients. Up to 24 subjects will be enrolled in cohort 2. Recruitment is expected to begin in 4Q2020 and the planned enrollment period is 36 months.

Esophageal cancer is the eighth most common cancer type and the sixth most common cause of cancer deaths worldwide. The 5-year survival rate in the US is 20%, and 10% in Europe3.

The esophageal cancer trial is an open-label, single-arm, prospective phase I study consisting of two parts: (i) dose-escalation to determine the RP2D of NBTXR3 activated by radiation therapy with concurrent chemotherapy, as per standard of care; and (ii) expansion at the RP2D with toxicity monitoring.

The patient population will include adults (age ≥ 18 years) with stage II-III adenocarcinoma of the esophagus that are treatment naïve and radiographically non-metastatic at screening. Up to 24 subjects will be enrolled. Recruitment is expected to begin in 4Q2020 and the planned enrollment period is 24 months.

Next Steps for Clinical Collaboration with MD Anderson

The clinical collaboration between Nanobiotix and MD Anderson includes plans for additional clinical trials across several indications. Beyond the three (3) trials mentioned above, the other trials, including four (4) combination trials with immune checkpoint inhibitors and NBTXR3 activated by radiation therapy, are in preparation and will launch in due time.

About NBTXR3

NBTXR3 is a novel 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 13, 2020 Seagen Inc. (Nasdaq: SGEN) reported that it will report its third quarter 2020 financial results on Thursday, October 29, 2020 after the close of U.S. financial markets (Press release, Seattle Genetics, OCT 13, 2020, View Source [SID1234568408]). Following the announcement, Company management will host a conference call and webcast discussion of the results and provide a general corporate update. Access to the event can be obtained as follows:

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Thursday, October 29, 2020
1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time

Telephone 844-763-8274 (domestic) or +1 412-717-9224 (international); conference ID 10148256
Webcast with slides available at www.seagen.com in the Investors section. A webcast replay will be archived on the Company’s website.

On October 13, 2020 Regulus Therapeutics Inc. (Nasdaq: RGLS) (the "Company" or "Regulus"), a biopharmaceutical company focused on the discovery and development of innovative medicines targeting microRNAs, reported receipt of a total of $5 million in milestone and material payments from Sanofi (Press release, Regulus, OCT 13, 2020, View Source [SID1234568404]). As outlined in the recent amendment to the Company’s term loan agreement with Oxford, LLC, the Company utilized the proceeds to pay down $5 million in principal outstanding, reducing the remaining principal due under the term loan to approximately $9.6 million.

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In August 2020, the Company entered into an amendment with Sanofi concerning the receipt of potential milestones from Sanofi for its development of miR-21 programs. Under the terms of the amendment with Sanofi, the Company was eligible to receive $4 million upon the completion of transfer and verification of certain materials valued at an additional $1 million sold to Sanofi. In addition to this payment of $5 million received, the Company is eligible to receive an additional $5 million upon achievement of the interim enrollment milestone and $25 million upon the achievement of the development milestone.

Concurrently with this recent Sanofi amendment, the Company announced an amendment of its term loan agreement with Oxford, under which the Company is eligible for up to an additional seven months of interest only payments in the event the Company pays down an additional $5 million in loan principal before April 30, 2021. In the event the Company receives the additional interest only period, principal and accrued interest payments will commence on January 1, 2022.

On October 13, 2020 Lantern Pharma (NASDAQ:LTRN) reported that it is using its RADR AI platform to identify abandoned drug candidates and develop new drugs that may prove effective in treating certain cancers (Press release, Lantern Pharma, OCT 13, 2020, View Source [SID1234568403]).

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"Our vision is to bring cancer therapies to market faster, and with reduced cost and risk, to ultimately improve patient outcomes," Panna Sharma, Lantern’s president and CEO, says in an interview with BioTuesdays.com. "We are employing a dual approach, developing both de novo biomarker-guided drug candidates and rescuing historical drug candidates by leveraging the datasets and machine learning algorithms in our RADR AI platform."

RADR was developed to predict drug responses and outcomes using interrelated biomarker and clinical data. The platform has curated and analyzed more than 500-million data points, including more than 140 cancer drug-tumor interactions. Mr. Sharma says that Lantern aims for RADR to become the largest AI-enabled oncology drug development platform. The company plans to capture more than one-billion data points by early 2021 and five-billion data points during 2022.

"The increasing availability of large-scale biomarker, genomic and patient data – and rapidly maturing technologies like AI and machine learning – means that the field of oncology is undergoing a monumental shift in the way cancer drugs are discovered, developed, studied, targeted, and commercialized. Lantern is at the forefront of this transformation," he contends.

The company’s pipeline, which was developed using RADR, consists of three oncology drugs that are being developed for four indications. Two of Lantern’s drug candidates are in Phase 2 of development, with the third currently in preclinical development. "Our three compounds are in active development and are aimed at therapeutic areas potentially worth several billion dollars in global sales, many of which do not have therapeutic options today."

Lantern’s first candidate, LP-100, or irofulven, is a DNA damaging agent originally developed at the University of California San Diego. The drug candidate was licensed to MGI Pharma, which was subsequently acquired by Eisai (TYO:4523), but its development was discontinued after endpoints in a Phase 3 trial for the treatment of metastatic pancreatic cancer did not exceed the survival benefits seen with the comparator agent, fluorouracil.

When Lantern acquired LP-100, it had been evaluated in more than 40 clinical trials across 13 different solid tumor types and demonstrated efficacy and strong anti-tumor benefit in subsets of patients.

"We acquired the small molecule with the goal of using biomarkers to predict which patients would best respond to the treatment," Mr. Sharma recalls, adding that early versions of RADR guided the development of an RNA-based genomic signature to determine patients’ response and sensitivity to LP-100.

In 2016, Lantern out-licensed LP-100 to Oncology Venture, which is now conducting a Phase 2 trial in patients with hormone refractory prostate cancer. Oncology Venture is using Lantern’s biomarker technology to identify and monitor patients, and expects to report data from the trial in 2021.

Lantern acquired its second drug candidate, LP-300, from BioNumerik Pharmaceuticals, in 2018. Also known as Dimesna, LP-300 is a chemosensitizer for use in combination therapies, with properties that reduce the toxicity associated with chemotherapy. LP-300 had been evaluated in five early- and five late-stage clinical trials for the treatment of lung and breast cancers.

Specifically, BioNumerik’s Phase 3 trial of LP-300, in combination with paclitaxel and cisplatin, did not meet clinical efficacy endpoints but demonstrated survival benefits in specific patient subgroups. Retrospective analyses showed that among 66 female non-smokers, those in the LP-300 study arm demonstrated a 125% relative two-year survival increase, compared with those who received only paclitaxel and cisplatin.

Lantern is using its RADR platform to develop a biomarker signature that can be used to predict which non-small cell lung cancer patients are most likely to respond to a combination therapy of taxanes, platin-based chemotherapy and LP-300. The company plans to initiate a Phase 2 clinical trial of LP-300 in the second half of 2021, in patients with non-small cell lung cancer, who have a history of no smoking, or have never smoked.

"The core RADR engine can generate a very robust biomarker or genomic signature that can eventually be used to both accelerate and guide preclinical development, and as a companion diagnostic to help enroll, stratify, and select patients that have the greatest potential to benefit from our therapy," Mr. Sharma points out.

Lantern’s third drug candidate, LP-184, is an acylfulvene-based compound with broad anti-tumor activity. LP-184 is currently in preclinical development for the treatment of genomically-defined solid tumors that can occur at any location in the body. Using RADR and cancer cell line gene expression profiles from the NCI-60 – a group of 60 human cancer cell lines used by the National Cancer Institute to screen compounds for potential anticancer activity – Lantern has derived a panel of 16 genetic biomarkers that are predictive of a response to LP-184.

In collaboration with Georgetown University, the company has done extensive wet-lab work in organoids, patient-derived xenograft models and genomically-edited cell lines where the signature continues to be refined across a range of solid tumors and CNS cancers. Lantern and Georgetown are entering the second phase of their ongoing development partnership, which will focus on a larger set of patient-derived xenograft models to further characterize LP-184’s mechanism of action, and on validating the role genetic biomarkers play in the drug candidate’s potency.

The company recently partnered with Philadelphia-based Fox Chase Cancer Center for the further development of LP-184 for the treatment of pancreatic cancer. The collaboration aims to create a more biologically relevant and robust gene signature in preparation for future clinical trials.

Lantern also is developing LP-184 for the treatment of glioblastoma multiforme, an aggressive form of brain cancer, as the compound has demonstrated high nanomolar potency in cell lines and an ability to penetrate the blood-brain-barrier. The company is currently conducting IND-enabling studies and plans to enter the clinic with LP-184 in late 2021 or early 2022.

"We are generating many meaningful and targeted insights using our RADR AI engine, in combination with targeted 3D and organoid studies, and are confident that we can accelerate the development efforts with certain abandoned or stalled compounds. Our goal is to add at least one additional oncology development program each year through a partnership, collaboration, or in-licensing agreement," he says.