On September 25, 2020 Shanghai Bangyao Biotechnology Co., Ltd. (BIORAY LABORATORIES Inc. "BIORAY LABORATORIES Inc."), a company focused on gene therapy and cell drug research and development, reported for the first time its cooperation with the First Affiliated Hospital of Zhejiang University School of Medicine The "PD1 knockout non-viral targeted integration of CD19-CART cells for the treatment of relapsed and refractory non-Hodgkin’s lymphoma clinical trials" achieved breakthrough results (Press release, Shanghai Bioray Laboratory, SEP 25, 2020, View Source [SID1234567717]). This is the world’s first use of gene editing technology to achieve targeted integration of CART therapy at the PD1 site, and it is also the world’s first clinical trial of non-viral targeted integration of CART cells to treat lymphoma. At the same time, the latest research results were announced on the preprint platform medRxiv on September 23, 2020, jointly completed by East China Normal University, the First Affiliated Hospital of Zhejiang University School of Medicine, and Shanghai Bangyao Biotechnology.

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The CD19-CART integrated by PD1 is a CART product obtained by Bangyao Biologics using the Quikin CART platform technology of independent intellectual property rights without using viral vectors. This product combines PD1 immune checkpoint suppression and CART tumor killing functions into one, which has the effect of combined application of PD1 immunotherapy and CART therapy.

2 patients in complete remission after 3 months of treatment

The clinical research plan enrolled 15 patients. The 4 patients that have been evaluated have achieved partial remission (PR) at 1 month, and 2 patients who have reached the evaluation time of 3 months have achieved complete remission (CR). ).

The first patient who achieved complete remission was diagnosed with diffuse large B lymphoma stage IVBE in 2018. After multiple radiotherapy and chemotherapy, the condition has not been effectively controlled. Before enrollment, imaging showed that the size of the mesangial space of the left lower abdominal small intestine was 3.6*3.5cm, and the radioactive uptake was abnormally increased. In May 2020, he was enrolled in the group for PD1 knockout non-viral targeted integration of CD19-CART cells for reinfusion therapy. PET-CT imaging showed that FDG metabolism was significantly lower than before 28 days after treatment, reaching PR. PET-CT after 90 days of treatment Imaging revealed that all the lesions disappeared, and FDG metabolism did not increase, reaching CR.

During the entire CART treatment process, no adverse events above grade 3 occurred, including cytokine storm and neurotoxicity. After reinfusion, CART expanded well in the body and lasted for a long time. The d90 flow cytometry showed that the CART cells in the peripheral blood remained at a certain proportion. At present, 2 patients have recovered and been discharged and are still undergoing long-term follow-up.

Comparison of imaging examinations before and after treatment

The principal investigator (PI) of the clinical study (PI), Dean of Huanghe, the First Affiliated Hospital of Zhejiang University School of Medicine, said : "Diffuse large B-cell lymphoma is the most common type of non-Hodgkin’s lymphoma. Lack of effective treatment. This year we began to explore the clinical research of non-viral targeted integrated CART based on gene editing technology. We are very pleased to see that patients quickly achieve complete remission after treatment. We expect this new CART technology will be difficult Treating relapsed patients will bring more convenient, safe and accurate long-term treatment effects."

Bangyao Bio-CART is upgraded to version 2.0, which is more effective and safer!

Bangyao Biotech’s non-viral targeted integration CART technology (Quikin CART) can use CRISPR/Cas9 gene editing technology to insert CAR elements into specific locations in the genome without using viral vectors, achieving gene knockout in one step Stable integration with CAR is a pipeline product of Bangyao Biology 2.0 version of CART.

PD-L1/PD1 is an important immune checkpoint for inhibiting T cell function. At present, PD-L1/PD1 inhibitors have achieved good efficacy in many types of malignant tumors, and many studies have reported PD1 knockout Can effectively enhance the function of CART cells. Non-Hodgkin’s lymphoma is a hematological malignant tumor that originates in the lymphatic tissues, accounting for 80%-90% of all lymphomas. Although the disease is relieved after the initial treatment, the patient often relapses afterwards. Although CART products have been approved for the clinical treatment of relapsed and refractory non-Hodgkin’s lymphoma, the overall efficacy is still limited, and studies have suggested that inhibiting the PD1 pathway may bring better clinical results.

Therefore, Bangyao Biosciences developed non-viral PD1 targeted integration of CD19-CART cells using Quikin CART platform to carry out clinical treatment of relapsed and refractory non-Hodgkin’s lymphoma. This product has the two major advantages of uniform and stable expression of CAR and PD1 gene knockout, which is equivalent to the combination of PD1 inhibitor and CART cells. In many clinical trials that have been carried out so far, the CART product has demonstrated excellent safety and effectiveness.

The preparation of traditional CART products mainly uses viral vectors, which puts forward high requirements on the virus preparation process, which greatly increases the manufacturing cost and difficulty of CART cells, and hinders the large-scale clinical application of CART treatment; and the price is very expensive, as currently For CART products on the market, Novartis’ Kymriah is priced at US$475,000, and Kite’s Yescarta is priced at US$373,000. In addition, because the virus uses random insertion to integrate CAR elements into the cell genome, it may change the expression of normal genes. The safety hazards of cancer. Quikin CART technology does not require the use of viral vectors for cell preparation, which greatly reduces the production cost of CART products and avoids the risk of cancer by random insertion.

Quikin CART technology can simultaneously realize the regulation of T cell endogenous genes and the continuous expression of CAR in one step. Compared with other CART technology, it has the advantages of simple process, fewer production links, short preparation time, and high product uniformity. This technology platform can be used for the preparation of multiple immune checkpoint knockout enhanced CART cells, rapid production of universal CART cells, and the development of dynamically regulated safe CART products, etc., providing a strong foundation for the diversified transformation of CART cells in the future. Strong technical support.

Professor Liu Mingyao, Chief Scientist of Bangyao Biosciences , East China Normal University, said : "Compared with traditional autologous CART technology, Quikin CART technology can achieve the targeted integration of CAR elements in the genome in one step without the use of viruses. Regulation and intervention of endogenous genes in T cells. This means that the preparation process, production links, and preparation time of CART cells will be greatly simplified and shortened, thus greatly reducing the production cost of CART cells and reducing tumorigenicity caused by random insertion of viruses Risks have also improved the uniformity of CART products. The current results show that the non-viral PD1 site-specific integration of CD19-CART cells prepared by us has great therapeutic potential and has shown good safety and remission rates in clinical trials."

Dr. Zhang Jiqin, the main person in charge of the project, the first author of the paper, the R&D director of Bangyao Bio-Innovation CART, and the associate researcher of the School of Life Sciences of East China Normal University, said: "In recent years, the continuous maturity and development of CRISPR/Cas9 gene editing technology has given us birth. Applying it to the idea of ​​CART therapy. Through an in-depth analysis of the existing CART technology problems, we realized that the use of gene editing technology to prepare non-viral targeted integration of CART cells is a very promising direction. Through a large number of methods to try and After exploring the conditions, we have established a mature Quikin CART technology platform. This technology does not require the use of any virus, and can produce CART cells in one step. It has many advantages that cannot be compared with the existing CART technology. Looking forward to using this technology platform in the future We can develop more successful CART products and make greater breakthroughs in clinical treatment."

It is reported that in addition to the ongoing non-viral PD1 targeted integration of CD19-CART clinical research, Bangyao Biosciences is also deploying other non-viral targeted integration of CART products for solid tumors in order to achieve greater breakthroughs in CART therapy.

On September 25, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported that the European Commission (EC) has granted conditional marketing authorization to AYVAKYT (avapritinib) as a monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation. For the first time in Europe, there is an approved therapy for patients with PDGFRA D842V mutant GIST specifically designed to target the underlying molecular driver of their disease (Press release, Blueprint Medicines, SEP 25, 2020, View Source [SID1234565614]).

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The EC approval is based on efficacy results from the Phase 1 NAVIGATOR trial as well as combined safety results from the NAVIGATOR and Phase 3 VOYAGER trials. AYVAKYT demonstrated deep and durable clinical activity and was generally well-tolerated in patients with PDGFRA D842V mutant GIST with or without prior therapy. In 38 NAVIGATOR trial patients with PDGFRA D842V mutant GIST at a starting dose of 300 mg or 400 mg once daily, AYVAKYT had an overall response rate (ORR) of 95 percent (95% CI: 82.3%, 99.4%), with 13 percent of patients achieving a complete response, and the median duration of response (DOR) was 22.1 months (95% CI: 14.1 months, not estimable). The median progression-free survival (PFS) was 24 months, and the median overall survival (OS) was not reached. These efficacy data were reported earlier this month during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020. The most frequently reported adverse reactions (≥20 percent) were nausea, fatigue, anemia, periorbital edema, face edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, decreased appetite and memory impairment.

GIST is a genomically driven sarcoma of the gastrointestinal (GI) tract, with PDGFRA D842V mutations implicated in a rare subset of patients. A retrospective study of patients with PDGFRA D842V mutant GIST showed that treatment with imatinib, the standard first-line GIST therapy, led to an ORR of 0 percent.2 ESMO (Free ESMO Whitepaper) guidelines recommend including mutational testing in the GIST diagnostic work-up as standard practice.

"There have historically been no treatments offering hope for patients with PDGFRA D842V mutant GIST. AYVAKYT represents the first major therapeutic breakthrough for patients with GIST harboring this mutation, defining a new standard of care," said Sebastian Bauer, M.D., medical oncologist at the West German Cancer Center in Essen, and an investigator on the NAVIGATOR trial. "The NAVIGATOR trial confirmed that almost all patients with PDGFRA D842V mutant GIST achieved tumor shrinkage and clinical responses were durable. These patients have lived longer than what is expected based on historical outcomes, and side effects have been well-tolerated in most patients. With this approval, it is more important than ever to conduct mutational testing prior to first-line treatment, so that patients with PDGFRA D842V mutant GIST may begin therapy with AYVAKYT, the only effective treatment for their tumor type."

"This year, Blueprint Medicines has received three marketing approvals globally, highlighting our commitment to rapidly advance a portfolio of transformative treatments and effectively deliver them to patients worldwide," said Jeff Albers, Chief Executive Officer at Blueprint Medicines. "AYVAKYT is the first highly active treatment option for PDGFRA D842V mutant GIST, offering much-needed hope for this rare patient population who have long been underserved by existing therapies. As we progress toward our AYVAKYT launches in Europe, we are focused on raising awareness about the therapy’s differentiated clinical profile and the importance of mutational testing, and working closely with health authorities to enable patient access to AYVAKYT as rapidly as possible."

In Europe, Blueprint Medicines plans to initiate its first commercial launch in Germany following the EC approval, and the timing of AYVAKYT availability will vary for other countries based on local reimbursement and access pathways. AYVAKYT will be available in 100 mg, 200 mg and 300 mg dose strengths, and the recommended starting dose is 300 mg once daily. As part of the conditional marketing authorization, Blueprint Medicines plans to conduct an observational, long-term study in patients with PDGFRA D842V mutant GIST treated with AYVAKYT.

"The introduction of a new targeted therapy, AYVAKYT, is an important milestone for patients with PDGFRA D842V mutant GIST, who have historically had no effective treatment options," said Markus Wartenberg, chair of Sarcoma Patients EuroNet Association (SPAEN). "We appreciate working with companies like Blueprint Medicines to advance treatment for those living with GIST, and empower the patient community through education and support."

About AYVAKYT (avapritinib)

AYVAKYT (avapritinib) is a kinase inhibitor approved in the EU for the treatment of adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. AYVAKYT is the first precision therapy approved in Europe to treat a genomically defined population of patients with GIST. The EC previously granted orphan medicinal product designation for AYVAKYT for the treatment of GIST. This medicine was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with unresectable or metastatic GIST harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations, under the brand name AYVAKIT.

This therapy is not approved for the treatment of any other indication in the U.S. or Europe, or for any indication in any other jurisdiction by any other health authority. It is being developed globally for the treatment of advanced and indolent systemic mastocytosis (SM). The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of aggressive SM, SM with an associated hematologic neoplasm and mast cell leukemia.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for avapritinib in the rest of the world.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the GI tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

About 5 to 6 percent of primary GIST cases are caused by a PDGFRA D842V mutation, the most common PDGFRA exon 18 mutation. Published data have shown poor outcomes in patients with PDGFRA D842V mutant GIST treated with imatinib and other approved therapies, including a median OS of 15 months, a median PFS of 3 months and an ORR of 0 percent.2

On September 25, 2020 Genelux Corporation, a privately-held clinical-stage immunotherapy company, reported that it has entered into a convertible note and warrant financing transaction with Woodward Diversified Capital (WDC) (Press release, Genelux, SEP 25, 2020, View Source [SID1234567101]). Genelux and WDC have completed the first close of a private placement of unsecured convertible notes of up to $20M and associated warrants.

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The transaction underscores the strength and promise of Olvi-Vec, Genelux’s lead oncolytic immunotherapy candidate. The Company intends to use the proceeds from the financing primarily to finalize preparations for and initiate its planned Phase 3 (registration) trial of Olvi-Vec in platinum refractory/resistant ovarian cancer and to fund further expansion of our clinical program, and for general corporate purposes.

Gabe Woodward, Partner at WDC, commented, "We were attracted to Genelux because of the caliber of the team and because they meet our criteria of having a breakthrough and innovative approach to address a significant unmet medical need."

"Genelux is fortunate to have the financial and sophisticated strategic support of WDC as we successfully advance Olvi-Vec towards its first registration trial," said Thomas Zindrick, J.D., President and CEO of Genelux.

About Olvimulogene Nanivacirepvec (Olvi-Vec)
Olvi-Vec is a proprietary, non-pathogenic oncolytic vaccinia virus, modified to increase its safety, tumor selectivity and anti-tumor activity. Virus-mediated oncolysis results in immunogenic cell death and triggers immune activation and memory for long-term immunotherapy against cancer. Clinical results in more than 150 subjects have shown Olvi-Vec is well tolerated with documented clinical benefits.

On September 25, 2020 RemeGen Co., Ltd. ("RemeGen") reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for disitamab vedotin (RC48), a novel humanized anti-HER2 antibody drug conjugate (ADC), for the second-line treatment of patients with HER2 positive locally advanced or metastatic urothelial cancer (UC) who have also previously received platinum-containing chemotherapy treatment (Press release, RemeGen, SEP 25, 2020, View Source [SID1234567622]). Earlier this year, RemeGen announced the FDA’s clearance of an Investigational New Drug (IND) application for a Phase II clinical study in the United States and the grant of Fast Track designation for disitamab vedotin.

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A drug development program with Breakthrough Therapy designation is eligible for all Fast Track designation features, intensive guidance on an efficient drug development program beginning as early as Phase I, and organizational commitment involving senior managers. This process is designed to expedite the development and review process.

"An estimated 81,400 new cases of urothelial cancer and 17,980 deaths are predicted in the United States in 2020i," said Jianmin Fang, Ph.D., founder, CEO and CSO of RemeGen. "The high prevalence of metastatic urothelial cancer underscores the need for effective and accessible treatment methods for patients. This Breakthrough Therapy designation will bring RemeGen one step closer to finding a safe and effective treatment for this devastating disease. We look forward to working with the FDA to advance the clinical development of disitamab vedotin."

Urothelial cancer represents the ninth most common cancer worldwide and the fourth most common cancer in men in the United States.ii

About RC48
RC48 was developed to treat HER2 expressing solid tumors. It has a novel antibody with a higher affinity to HER2 compared to standard of care, and superior anti-tumor activity compared to other treatments in animal models. RC48 was the first ADC drug approved for human clinical trials in China and favorable safety profile has been observed in clinical trials. It is currently being studied in multiple late-stage clinical trials across solid tumor types.

On September 24, 2020 Selecta Biosciences, Inc. (NASDAQ: SELB), a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance platform, ImmTORTM, reported that Selecta’s Chief Executive Officer, Carsten Brunn, Ph.D., will participate virtually in the following investor conferences in October (Press release, Selecta Biosciences, SEP 24, 2020, View Source [SID1234565579]):

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Jefferies Virtual Gene Therapy/Editing Summit
Date: Thursday, October 1, 2020
Fireside chat time: 4:30 p.m. ET

Chardan Virtual 4th Annual Genetic Medicines Conference
Date: Monday, October 5, 2020
Fireside chat time: 2:30 p.m. ET

Live webcasts will be available in the Investors & Media section of the company’s website at www.selectabio.com.