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Two Issued U.S. Patents Granted to Cellectis for CRISPR Use in T-Cells

On February 13, 2018 Cellectis (Paris:ALCLS) (NASDAQ:CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported the issuance of two U.S. patents – US 9,855,297 and US 9,890,393 – for the invention of certain uses of RNA-guided endonucleases, such as Cas9 or Cpf1, for the genetic engineering of T-cells (Press release, Cellectis, FEB 13, 2018, View Source [SID1234523941]). The patents came into force on January 2nd, 2018 and February 13th, 2018, respectively.

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Both patents claim methods by which T-cells are gene edited using transient expression of CRISPR/Cas9 components. These inventions are based on the early work initiated by inventors at Cellectis when the CRISPR technology first came to light.

These therapeutic-focused patents follow the grant by the European Patent Office of patent No. EP3004337 for similar inventions and previous intellectual property that Cellectis has obtained over the last two decades for major gene editing technologies including meganucleases, TALEN, MegaTAL and CRISPR.

"Cellectis is a pioneering gene editing company that has always been keen to be at the forefront of all gene editing technologies," said Dr. André Choulika, Cellectis Chairman & CEO. "We have been the first to explore the potential of CRISPR in its early days in various applications, including therapeutics and plants. These early findings ultimately led to the grant of this set of new patents. As such, these patents only reinforce Cellectis’ leadership position in the gene editing industry."

Convinced of their strong value for the future development of engineered CAR T-cells, Cellectis will make these patents available for licensing to companies that are willing to use CRISPR technologies in T-cells. The technical knowledge in these patents could, for example, help users engineer allogeneic CAR T-cells while suppressing genes involved in checkpoint inhibitions, such as PD-1, engineer drug resistance, or remove MHC (Major Histocompatibility Complex) related genes. The technology could also be used to insert a DNA CAR construct by gene targeting a specific locus in the genome of T-cells.

The inventors of these patents are Dr. André Choulika, Chairman & CEO of Cellectis and one of the pioneers in the development of nuclease-based genome editing technologies; Dr. Philippe Duchateau, Cellectis Chief Scientific Officer and seasoned gene editing expert; and Dr. Laurent Poirot, Cellectis Head of Early Discovery and expert of gene functions in immune cells.

Claims 1 and 2 of US 9,855,297:

1. A method of preparing genetically modified primary T-cells for immunotherapy comprising the steps of: (a) transfecting mRNA encoding an RNA-guided endonuclease into the primary T-cells, wherein the RNA-guided endonuclease is expressed from the transfected m RNA; (b) introducing a DNA vector that encodes a specific guide RNA, wherein the specific guide RNA directs the RNA-guided endonuclease to at least one targeted locus in the T-cell genome into the primary T-cells; (c) cleaving at least one targeted locus in the T-cell genome with the RNA-guided endonuclease; (d) generating a genetic modification at the site of the cleavage; and (e) expanding the resulting genetically modified T-cells.

2. The method of claim 1, wherein the RNA-guided endonuclease is Cas9.

Claim 1 of US 9,890,393:

1. A method of preparing T-cells for immunotherapy comprising the step of:

(a) genetically modifying primary T-cells by introduction and/or expression into the cells of at least:

– a RNA-guided endonuclease; and

– a specific guide RNA that directs said endonuclease to at least one targeted locus in the T-cell genome,

wherein said RNA-guided endonuclease is expressed from transfected mRNA;

wherein said RNA-guided endonuclease comprises the amino acid sequence set forth in SEQ ID NO:1 or SEQ ID NO:2; and

(b) expanding the resulting cells.

Athenex Announces Recent Product Launches in 503B and Specialty Injectables Business Units

On February 13, 2018 Athenex, Inc. (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported recent product launches from Athenex Pharmaceutical Division ("APD") (Press release, Athenex, FEB 13, 2018, View Source;p=RssLanding&cat=news&id=2332087 [SID1234523939]). These launches highlight the continued portfolio growth with an emphasis on oncology or oncology supportive therapy, a business strategy of Athenex’s commercial business as an effective supplement to its progressing clinical pipeline focused on oncology.

Athenex has brought the following products to market in its 503B (outsourced sterile preparations) and Specialty (finished-dose specialty injectable products) businesses:

503B Products

Epinephrine 2 mg and 4 mg in 250 mL in 0.9% Normal Saline (2 SKUs)
Norepinephrine 4 mg and 8 mg in 250 in 0.9% Normal Saline (2 SKUs)
Specialty Products

Caspofungin Acetate for Injection 50 mg per vial; 70 mg per vial (2 SKUs; vials)
Doxorubicin 5 mL, 25 mL, 100 mL; (3 SKUs; vials)
Etomidate Injection 20 mg per 10 mL; 40 mg per 20 mL; (2 SKUs; vials)
Gemcitabine for Injection 1 mg (1 SKU; vials)
Paclitaxel Injection 30 mg per 5 mL; 100 mg per 16.7 mL; 300 mg per 50 mL; (3 SKUs; vials)
Jeffrey Yordon, Athenex’s Chief Operating Officer and President of APD, commented, "These product launches underscore a continuation of our ongoing commitment to bring needed, quality oncology products to market on both the 503B and Specialty Injectables sides of our business. As part of a broader effort to build our commercial platform and capabilities, we will continue to look for opportunities to bring additional products focused mainly on oncology and oncology supportive care therapies to our customers throughout 2018 as well as generate additional revenue to help fund our clinical programs."

Athenex is committed to quality and product labeling innovation. cGMP processes are followed for each of Athenex’s products, and a Certificate of Analysis is provided for each batch of 503B products so customers are able to see measurable results from repeatable tests. Additionally, Athenex’s AccuraSEE, a proprietary and highly differentiated approach to package and labeling, has a unique design to give caregivers accurate information and reduce the risk of medication errors.

Advaxis Submits Conditional Marketing Authorization Application for Axalimogene Filolisbac for the Second-Line Treatment of Metastatic Cervical Cancer in European Union

On February 13, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of cancer immunotherapies has submitted a conditional Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the company’s lead Lm Technology product candidate, axalimogene filolisbac, for the treatment of adult women who progress beyond first-line therapy of persistent, recurrent or metastatic carcinoma of the cervix (PRmCC).

"The submission of the MAA represents a significant regulatory milestone for Advaxis and the ongoing development of our Lm Technology Platform," stated Anthony Lombardo, interim Chief Executive Officer of Advaxis. "The submission is based on the improvement in 12-month survival rates observed in the Phase 2 GOG-0265 study. We feel that these data support axalimogene filolisbac as a potential therapeutic option for patients living with PRmCC who are in desperate need of new treatment options beyond first-line therapy," added Lombardo.

The MAA submission is built around data from the GOG-0265 study which examined overall survival rates in 50 women and showed a 12-month overall survival rate (primary efficacy endpoint) of 38% (n=19/50) in women with PRmCC, representing a 55% improvement over an expected, model-predicted,12-month survival rate of 24.5%.2 More than 50% of treated women in this study had previously received multiple prior lines of therapy including treatment with bevacizumab and subsequently experienced progression of their disease.2

"Despite the availability of preventative measures, metastatic cervical cancer continues to be a major public health concern associated with high mortality rates within Europe," said Mansoor Mirza, M.D., Chief Oncologist at the Copenhagen University Hospital in Denmark and Medical Director of the Nordic Society of Gynaecological Oncology (NSGO). "The results from GOG-0265 are encouraging and could represent a meaningful step forward in the care of women suffering from PRmCC, which has seen very little innovation in almost 30 years."

In the GOG-0256 study, axalimogene filolisbac was generally well-tolerated with mostly Grade 1 and 2 flu-like adverse events associated with cytokine release which were managed with standard medical care. This safety profile is consistent with the ongoing clinical experience of axalimogene filolisbac across all clinical trials.

The EMA will evaluate the totality of the data, including results from GOG-0265 as well as supportive data from other clinical trials evaluating axalimogene filolisbac. In parallel with the MAA review process, the company will continue assessing partnership opportunities for the potential commercialization of axalimogene filolisbac in Europe.

The company has also decided to align and simplify its strategy by using axalimogene filolisbac exclusively in all ongoing and planned HPV-related cancer clinical trials, including the upcoming ADVANCE trial, previously planned with ADXS-DUAL. The strategic decision to harmonize all trials to axalimogene filolisbac is based on its clinical profile to date in over 250 patients, and its demonstration of similar activity in both HPV 16 and 18 subtypes in GOG-0265. The company believes that harmonizing to a single product candidate for all HPV-related programs will streamline developmental, regulatory and commercialization strategies.

About Axalimogene Filolisbac

Axalimogene filolisbac is a targeted Listeria monocytogenes (Lm)-based investigational immunotherapy that attacks HPV-associated cancers by altering a live strain of Lm bacteria to generate cancer-fighting T cells against cancer antigens while neutralizing the tumor’s natural protections that guard the tumor microenvironment from immunologic attack.

Axalimogene filolisbac has already achieved multiple regulatory milestones, including classification as an EMA advanced therapy-medicinal product for the treatment of cervical cancer, receipt of the U.S. Food and Drug Administration (FDA) Fast Track Designation as an adjuvant therapy for treating high-risk, locally advanced cervical cancer (HRLACC), receipt of a Special Protocol Assessment agreement with the FDA for the Phase 3 AIM2CERV trial, and orphan drug designations in three HPV-associated indications (PRmCC, head and neck, and anal cancer). In addition, axalimogene filolisbac will be studied in combination with nivolumab in the ADVANCE trial, a potential registrational trial for patients with PRmCC, which is planned to begin in 2018.

Frontier Fighter of Brain Tumor

Glioblastoma multiforme is the most common and deadliest of the glial tumors because it is hard to cure with a very high possibility of recurring. Diffuse intrinsic pontine glioma (DIPG) is a sub-kind of glioblastoma that mainly affects children. It has a 5-year survival rate less than 1%.

According to the ABTA, there are nearly 700,000 people in the United States living with a primary brain and central nervous system tumor. Of these, 14.9 percent are glioblastomas. There is an estimated of 12,390 new cases predicted in 2017.
ACT001 is a drug designed and developed by Accendatech specifically used to target brain tumor for treatment of GBM and DIPG

ACT001
ACT001 is an investigational product currently finished testing in phase 1 clinical studies.

MOLOGEN Signs License Deal for China and Global Co-Development Agreement with ONCOLOGIE for Lead Compound lefitolimod

On February 13, 2018 The biopharmaceutical company MOLOGEN AG (ISIN DE0006637200; Frankfurt Stock Exchange Prime Standard: MGN) reported the signing of a license deal for the Chinese territory and a global co-development agreement between MOLOGEN and ONCOLOGIE Inc. for its lead compound lefitolimod (Press release, Mologen, FEB 13, 2018, View Source [SID1234527267]). The signed agreement is conditional upon an initial payment of EUR 3 million received by MOLOGEN. ONCOLOGIE is an oncology-focused drug development company with headquarters in Boston and operations in Shanghai. The company is backed by top-tier international investors and has the objective to develop novel personalized medicines in the field of immuno-oncology. The signed agreement with ONCOLOGIE includes the development, manufacture and commercialization of lefitolimod in China and a planned global co-development program.

"We are delighted to partner our lead compound lefitolimod with ONCOLOGIE. Their approach of an innovative biomarker-driven development strategy for novel cancer immunotherapies has convinced us that partnering with them will expand the opportunities for success of lefitolimod. With the combined licencing and co-development deal for our flagship compound lefitolimod we have achieved one of the main milestones in implementing our strategy. In ONCOLOGIE we have found a partner with a highly dedicated and experienced international team who will not only drive lefitolimod development in China to achieve market approval but will also strongly support our global development efforts. Together we will strive to unleash lefitolimod’s full market potential in China and on a global level", said Dr Mariola Soehngen, Chief Executive Officer of MOLOGEN.

"We are happy to partner with MOLOGEN on lefitolimod, a best-in-class TLR9 agonist with exciting potential. This program complements ONCOLOGIE’s strategy for biomarker-driven global development and has multiple opportunities for treating indications prevalent in the Asian market", said Dr Laura Benjamin, Chief Executive Officer of ONCOLOGIE.

As previously announced, MOLOGEN had started negotiations on such a deal with the Chinese iPharma. After a certain exclusivity period had expired, MOLOGEN opened the licencing process also for additional parties. Discussions and negotiations with ONCOLOGIE have now been successfully completed and the deal could be signed. The terms of the signed agreement with ONCOLOGIE describe development, manufacture and commercialization of lefitolimod in China and a planned global co-development program.

The contract comprises two parts: First, a license agreement including sublicense rights under which MOLOGEN grants ONCOLOGIE an exclusive license for the development, manufacturing and commercialization for MOLOGEN’s lead compound lefitolimod in the following territory: China, Hong Kong and Macao, Taiwan and Singapore. Second, a commitment for global co-development leveraging novel biomarker plans from ONCOLOGIE. MOLOGEN is to receive an initial payment of EUR 3 million as well as a EUR 2 million equity investment by ONCOLOGIE within the next 12 months. Besides the initial payment and the equity investment, the parties agreed on further development and commercialisation milestones. They are due upon reaching predefined development steps as well as market approval. In addition, commercial milestones are defined which are due upon reaching certain sales thresholds. The total payments can amount to above EUR 100 million and will be paid over several years. Additionally, MOLOGEN will receive low double digit royalties on sales. MOLOGEN and ONCOLOGIE will share the economic returns from global joint development pursuant to both parties’ contributions.

All costs relating to development, registration, marketing and commercialization of lefitolimod in the territory are to be covered by ONCOLOGIE.