On December 14, 2022, Guangzhou Biosyngen Co., Ltd. (hereinafter as "Biosyngen") reported on the approval granted by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the company’s IND application for BRG01 Therapy (Press release, BioSyngen, DEC 14, 2022, View Source;c=View&a=index&aid=91 [SID1234631943]). BRG01 Therapy is an autologous T cell therapy for relapsed/metastatic nasopharyngeal cancer (NPC) treatment. The principle of autologous T cell therapy is to genetically modify patients’ own T cells to express additional receptors for Epstein-Barr virus (EBV) antigen recognition and T cell activation upon EBV+ tumor cell engagement.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The IND approval of BRG01 Therapy marks a significant milestone for the company and in nasopharyngeal cancer treatment." said Joan Zhang, Chairman of Biosyngen. "As a biopharmaceutical company in immunotherapy, Biosyngen is committed to deliver more effective cancer therapy to address unmet needs for the benefit of cancer patients. Following this milestone, based on the company’s pipeline, Biosyngen has begun planning for multiple sponsor-initiated clinical trials which will lead to IND applications in China, the US and Singapore in the course of 2023. The indications targeted are hepatocellular cancer, colorectal cancer, gastric cancer, esophageal cancer and pancreatic cancer. Looking ahead, Biosyngen is assessing the marco environment in preparation for IPO within the next 18 months."

About BRG01

EBV is a human herpesvirus and has infected ~95% of population worldwide. It has been listed as Group 1 carcinogen ("Carcinogenic to humans") by World Health Organization (WHO) and proved to be associated with a range of diseases including nasopharyngeal cancer, EBV-positive gastric cancers, lymphoma and lymphoproliferative diseases. As one of the most common head and neck tumors, nasopharyngeal cancer, an epithelial carcinoma arising from the nasopharyngeal mucosal lining, is closely related to EBV infection. According to WHO, an estimated number of 133,000 new cases of nasopharyngeal cancer worldwide was reported in 2020; 50% of which was diagnosed in China. South China provinces such as Guangdong and Guangxi provinces make up for more than 60% of nasopharyngeal cancer patient population.

Though, existing practice such as immune checkpoint inhibitor has been applied in second-line and beyond treatment of nasopharyngeal cancer, overall response rates were mostly below 30%. In another words, more than 70% patients did not benefit from the existing therapy. Therefore, it is imperative to explore new approaches to improve efficacy and satisfy unmet medical needs.

BRG01 Therapy developed by Biosyngen is an engineered T cell therapy, also known as a type of adoptive immune cell therapy for nasopharyngeal cancer treatment. Patients’ T cells were isolated and genetically modified in a GMP-compliant facility to enhance their ability to recognize and attack specific antigens on cancer cells. The modified T cells are expanded ex vivo and infused back into the patient. The infused T cells would bind to the specific antigen on the cancer cells to mediate tumor killing. The preliminary safety and efficacy of BRG01 Therapy have been demonstrated in data from exploratory clinical trials.

The scientific direction of Biosyngen is focused on targeting multiple solid tumors and hematological tumors. The company has independently developed a number of exclusive technical platforms specifically for cancer immunotherapy, including IDENTIFIER, SUPER-T and MSE-T. These platforms greatly improved the company’s capability to overcome challenges in antigen identification, antibody TCR screening and identification of immune cell function.

On December 14, 2022 Cofactor Genomics, the diagnostics company bridging the precision medicine gap, reported commencement of a study of its OncoPrism assay in non-small cell lung cancer (NSCLC), the second indication being studied in the company’s national PREDAPT study that will ultimately encompass 11 cancers (Press release, Cofactor Genomics, DEC 14, 2022, View Source [SID1234626579]). OncoPrism is the company’s diagnostic platform that generates multidimensional immune biomarkers using Predictive Immune Modeling. This approach has been shown to predict immunotherapy responders with twice the accuracy of on-market PD-L1 assays, with the added benefit of requiring far less tissue than most commercial tests.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

By better identifying patients who will likely respond to immunotherapy, Cofactor’s OncoPrism will spare more patients from chemotherapy and its negative side effects. The low input of tissue required for the test also makes it easier for lung cancer patients in whom a core needle biopsy is the safest option for acquiring tissue. Published results in Nature Scientific Reports show that Cofactor’s approach predicted patient response to anti-PD-1 therapy in lung cancer and outperformed the indicated PD-L1 test and Tumor Mutational Burden.

The PREDAPT (Predicting Immunotherapy Efficacy From Analysis of Pre-treatment Tumor Biopsies) Trial is evaluating use of the OncoPrism assay in effectively predicting a patient’s response to immunotherapy. To date, more than 20 healthcare systems have partnered with Cofactor in the study that will ultimately study 11 solid tumor cancers. The first indication opened for study was recurrent and metastatic squamous cell carcinoma of the head and neck (RM-HNSCC). HNSCC data presented at the AGBT Precision Health Meeting showed that Cofactor’s test is nearly twice as accurate as PD-L1 assays in determining patients that will benefit from immunotherapies, such as Keytruda (pembrolizumab) or Opdivo (nivolumab). Indications to be studied within the PREDAPT Trial include triple-negative breast, cervical, colorectal, esophageal, gastric, head and neck, kidney, liver, lung, and urothelial cancers.

"Lung cancer is the deadliest cancer in America, yet today less than 25 percent of cancer patients are matched to an immunotherapy that helps them. Our mission is to address that gap by leading the development of predictive diagnostics that can be a more effective matchmaker between patients and the treatments most likely to benefit them," said Sara Lapomarda, Director of Clinical Partnerships for Cofactor Genomics. "By studying our unique diagnostic approach in lung cancer, we hope to positively impact the trial-and-error approach to treating patients that can delay time to an effective treatment and spare them from unnecessary toxicities from chemotherapy in order to improve patient outcomes and survival for many. We intend to grow our clinical and biomarker team quickly to expedite validation of our lung cancer assay so it will closely follow our head and neck cancer assay in 2023."

About Predictive Immune Modeling

Predictive Immune Modeling (PIM) is Cofactor’s proprietary approach to immunotherapy predictive diagnostics. It is based on understanding the immune cell composition of a tumor, such as T cells, which has been shown to be predictive of immunotherapy response. It goes beyond testing individual markers by first building a model of the immune composition of patient responders to immunotherapy using 100+ RNA-based biomarkers processed with machine learning. Then, the company’s OncoPrism assay is used to compare a patient’s genetic profile to this model to determine how likely the patient is to be a responder themselves. This approach has been shown in published literature to be almost twice as accurate as the most commonly used biomarker, PD-LI, in identifying immunotherapy responders across a variety of cancers.

On December 14, 2022 (the "Execution Date") MacroGenics, Inc. (the "Company") entered into a Fifth Amendment (the "Amendment") to its existing lease agreement (the "Lease") with ARE-Maryland No. 45, LLC (the "Landlord"), for 122,600 square feet located at 9704 Medical Center Drive in Rockville, Maryland (the "Premises") (Filing, 8-K, MacroGenics, DEC 16, 2022, View Source [SID1234625356]). The Amendment provides for, among other things, an extension of the term of the Lease from August 15, 2027 to December 31, 2035, unless earlier terminated or extended (the "Modified Term"). During the Modified Term, base rent will be calculated annually on a per square foot basis, beginning at $46.37 per square foot and escalating annually by three percent thereafter. The Amendment also contains two options to extend the term of the Lease, which, if executed, would extend the lease to December 31, 2045. For a period of twenty-four months beginning on the Execution Date, the Landlord has granted the Company a rent abatement of fifty percent of the base rent payable for the Premises.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The foregoing description of the Amendment is not complete and is qualified in its entirety by reference to the Amendment, along with the original lease and amendments, which the Company intends to file as an exhibit to the Company’s Annual Report on Form 10-K for the fiscal year ending December 31, 2022.

On December 14, 2022 Ellipses Pharma ("Ellipses"), a global drug development company focused on accelerating the development of new oncology treatments, reported the first dosing of a patient in EP0031-101, a trial investigating Ellipses’ next generation selective RET inhibitor (SRI) EP0031 (Press release, Ellipses Pharma, DEC 14, 2022, View Source [SID1234625287]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

EP0031 is an SRI which aims to address the unmet need for patients with RET-altered tumours (Non-Small Cell Lung Cancer (NSCLC), medullary thyroid and other RET-altered tumours) who have progressed on first generation SRIs. This global, modular, Phase 1/2 trial will evaluate the safety, tolerability and efficacy of EP0031 in patients with advanced RET-altered tumours and is now open to enrolment at multiple US sites. Ellipses plans to open further trial sites in the UK and EU in 2023.

Developed in partnership with Sichuan Kelun-Biotech Pharmaceutical Co., Ltd (Kelun-Biotech), EP0031, known as A400 when in conjunction with Kelun-Biotech’s ongoing regional development, is already under clinical investigation in China for NSCLC and thyroid cancers. Kelun-Biotech continues to rapidly progress their clinical trial which is now in the dose expansion stage. Kelun will present clinical data for the first time at an international conference in 2023.

Prof Tobi Arkenau, Global Head of Drug Development & CMO, commented:

"Enrolment has started at UCLA, Portland Providence, MD Anderson and University of Kentucky and these will be joined by more sites in the next few months. There is an increasing number of patients whose cancers progress despite treatment with first generation SRIs, and as such EP0031 provides an exciting opportunity to address this unmet need."

Dr Rajan Jethwa, Chief Executive Officer & Founder of Ellipses, commented:

"EP0031 is a promising next generation SRI that seeks to address some of the issues with first generation SRIs. Dosing the first patient in this trial is an important first step for EP0031. Next generation SRIs offer the potential to expand the armamentarium against RET-driven cancers and further improve patient outcomes."

Dr Junyou Ge, Chief Executive Officer of Kelun-Biotech, commented:

"A400 (EP0031) offers a significant therapeutic potential for tumours with RET oncogene mutation/fusion and is hoped to bring new treatment options for patients. We are pleased that the EP0031-101 trial has dosed the first patient in the United States and congratulate our partner Ellipses on this important milestone. Kelun-Biotech will continue to collaborate with Ellipses to promote the global development and subsequent potential commercialisation of A400 to benefit more cancer patients around the world."

About EP0031 (A400)

EP0031 is a potent next generation SRI with broad activity against common RET fusions and mutations, including solvent front resistance mutations. Therefore, EP0031 (A400) may have the potential to overcome resistance to first generation SRIs. An IND application for EP0031 (A400) was approved by China’s National Medicinal Products Administration (NMPA) in June 2021 and a Phase 1/2 trial is ongoing in China. In March 2021, Kelun-Biotech granted Ellipses an exclusive license for EP0031 (A400) in certain territories including the US and Europe, with Kelun-Biotech retaining certain rights in Greater China and part of the Asia-Pacific region. In June 2022, the US FDA approved the EP0031 IND application, and the Ellipses Phase 1/2 trial is ongoing in the US.

About RET-altered cancers

It is estimated that RET fusions & mutations may be responsible for ≃2% of all cancers, this includes 2% of NSCLC, 60-80% of medullary thyroid cancers (MTC) and <1-20% across a range of other cancers.1 When patients progress on currently approved first generation SRIs there are limited treatment options and prognosis is poor.

On December 14, 2022 -CatalYm reported three major expansions of its ongoing Phase 2 visugromab clinical development program. Based on initial positive patient responses, the company is advancing two potential lead indication cohorts into the second stage of the Simon-2-stage design ahead of schedule (Press release, Catalym, DEC 14, 2022, View Source [SID1234625286]). Additionally, CatalYm is expanding its visugromab Phase 2 development program to include a new confirmatory cohort exploring the response-predictive biomarkers identified in the Phase 1.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Phase 2 study is evaluating visugromab in advanced-stage cancer patients that are relapsed or refractory to prior anti-PD-1/-PD-L1 treatment in a selected group of solid tumor indications. Based on early emerging responses in several major solid tumor indications, Catalym will enlarge the Phase 2 by expanding two cohorts as foreseen in the Phase 2 protocol. The persuasive responses seen in the study to date enable the expansion earlier than anticipated and before the original cohorts were fully enrolled. Combined with the clinical data generated in the Phase 1, these data further support the significant potential of visugromab in this PD-1 refractory solid tumor patient population.

In addition, CatalYm expanded its Phase 2 study with a newly established, tumor-agnostic, fully biomarker-selected cohort. This cohort aims to assess the prediction accuracy of response for two potential biomarkers in a total of 25 cancer patients treated with the GDF-15-targeting antibody visugromab in combination with the anti-PD1 antibody nivolumab in patients that are relapsed/refractory to prior anti-PD1/PD-L1 treatment. The two biomarkers were identified as part of the company’s stringent Phase 1 biomarker program where triple-biopsies were mandatory and evaluated regarding molecular and immunohistochemical parameters of significance. The company recently presented mature results from this Phase 1 dose escalation study at the 2022 ESMO (Free ESMO Whitepaper) congress.

"Our first indication-specific cohorts reaching the trigger for stage-2 enrolment before having completed enrolment of stage 1 is a clearly positive signal for the clinical potential of visugromab in advanced-stage, anti-PD1/PD-L1 relapsed/refractory cancer patients. In light of the highly promising phase 1 biomarker data, we now also added a fully biomarker-selected cohort to our program, to ideally confirm these early findings. This progress in the development of visugromab is exciting to see." stated Prof. Dr. Eugen Leo, Chief Medical Officer at CatalYm. "Identifying biomarkers that predict treatment outcomes is a critical endeavor in modern cancer medicine. The ability to identify the patients that will benefit most is a highly valuable additional asset for the future development of visugromab."

Dr. Phil L’Huillier, Chief Executive Officer at CatalYm added: "We have set up this Phase 2 program to confirm the potential clinical benefit of targeting GDF-15 in specific solid tumor indications. The new biomarker cohort and the first Simon-2-stage expansions will help us to gather valuable information for the future development of visugromab and should bring us significantly closer to registration trials. We are highly encouraged by the clear development opportunities unfolding in front of us which have also been validated through our recent oversubscribed Series C funding. Our path toward rapidly bringing this novel IO therapy to cancer patients is clear."

Recruitment for the biomarker expansion cohort has been initiated in Spain, Germany and Switzerland as part of the ongoing multi-center, open-label, GDFATHER-2 trial (NCT04725474). The Phase 2 part of the study, originally commenced in February 2022, is evaluating the treatment of GDF-15 neutralizing antibody, visugromab, in combination with the anti-PD-1 checkpoint inhibitor nivolumab in advanced stage cancer patients that are relapsed or refractory to prior anti-PD-1/-PD-L1 treatment. The study is planned to enroll up to 164 participants aged 18 years or older in up to 7 cohorts at major clinical centers across Europe and the United States. The biomarker-selected cohort will include broad tissue analyses, incorporating protein- and RNA-levels as well as analysis of the patient’s tumor immunogram which will be correlated with clinical outcomes. An initial data update from the first cohorts of the study is expected in mid 2023. CatalYm recently completed a €50 million Series C funding round to support the continued late-stage development of the program.