On December 20, 2018 Ayala Pharmaceuticals, Inc., a clinical-stage company developing medicines for cancers that are genetically identified, reported that it entered into an option to license agreement with Novartis for its investigational agent AL102 in multiple myeloma (Press release, Ayala Pharmaceuticals, DEC 20, 2018, View Source [SID1234532198]). Under the terms of the deal, Ayala will receive a $10 million equity investment from Novartis and is eligible to receive development, clinical, regulatory and commercial milestones along with tiered royalties on net sales of AL102.

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Novartis will conduct certain studies to evaluate AL102 in combination with its B-cell maturation antigen (BCMA) therapies in multiple myeloma. Ayala will provide the drug supply. All development costs associated with the above studies will be fully born by Novartis. Ayala retains worldwide license rights for AL102 for all other indications.

"We are extremely pleased to enter this agreement with Novartis on AL102. Novartis has a strong commitment and expertise in oncology, and a proven record of success in drug development, making them an ideal strategic partner for AL102 in multiple myeloma," said Roni Mamluk, PhD, chief executive officer at Ayala. "This collaboration is important to Ayala as it immediately strengthens our balance sheet, further validates our technology and accelerates the clinical development of AL102 as a combination therapy in hematologic cancers."

AL102 is an oral small-molecule that inhibits gamma secretase, an enzyme which may be targeted to increase levels of BCMA, which is expressed in most multiple myeloma patients. BCMA is actively shed from multiple myeloma cells by gamma secretase, hence its inhibition by AL102 may increase BCMA levels on multiple myeloma cells. Therefore, AL102 is being studied to evaluate its clinical role in enhancing anti-BCMA therapies.

Ayala is committed to developing new targeted therapies for genomically-defined cancers in patient populations with high unmet medical need. In addition to investigating AL102 as an anti-BMCA therapy in multiple myeloma, Ayala is evaluating AL102 as an inhibitor of the Notch pathway in other hematologic cancers.

Multiple myeloma is a rare and aggressive blood cancer that accounts for approximately one percent of all cancers. In the U.S., there are nearly 90,000 people living with, or in remission from, multiple myeloma. Approximately, 26,850 Americans are diagnosed with multiple myeloma each year and 11,240 patient deaths are reported on an annual basis.

On December 20, 2018 Novartis reported an offer to acquire CellforCure from LFB. CellforCure, a French company, is one of the first and largest contract development and manufacturing organizations (CDMO) producing cell and gene therapies in Europe (Press release, Novartis, DEC 20, 2018, View Source [SID1234532214]).

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Under the proposed agreement, Novartis would acquire the share capital of CellforCure from LFB including the cell and gene manufacturing facility located in Les Ulis and the related adjacent land. If the offer is accepted, CellforCure would become a wholly owned Novartis manufacturing site, joining the network of cell and gene therapy sites including Morris Plains, New Jersey, USA and Stein, Switzerland, where construction continues to progress as planned.

In July 2018, Novartis announced that it had signed an agreement with CellforCure to produce CAR-T cell therapies including Kymriah (tisagenlecleucel), the first CAR-T cell therapy approved by the United States Food and Drug Administration (FDA) and indicated for two distinct, difficult-to-treat cancers in the United States, European Union, Switzerland, Canada and Australia. Novartis and CellforCure have successfully completed technology transfer and Kymriah clinical supply production is expected to begin by mid-2019. The proposed acquisition of CellforCure is another example of continued commitment by Novartis to investing in cell and gene therapies as well as in France.

Novartis has made several steps recently to strengthen and expand its cell and gene manufacturing, including signing a strategic licensing, collaboration and share purchase agreement with Cellular Biomedicine Group (CBMG) to manufacture and supply Kymriah in China; expanding an alliance with the Fraunhofer Institute in Germany to support manufacturing for clinical trials and post approval manufacturing; and a contract manufacturing collaboration in Japan.

Novartis Global Head of Technical Operations Steffen Lang said, "The proposed acquisition of CellforCure is another strategic step in our pursuit of additional manufacturing capacity to make our transformational CAR-T cell therapy Kymriah available to more patients in need around the world. If completed, this acquisition also would potentially increase manufacturing capacity for other cell and gene therapies in the Novartis pipeline. We are excited about the possibility of adding the significant experience of CellforCure to our existing leadership in pioneering research, development and supply of cell and gene therapies."

The transaction is subject to usual and customary closing conditions, including employee consultation process and necessary regulatory approvals. If approved, the transaction is expected to be funded through available cash and close in the first half of 2019.

CellforCure is an LFB group company specializing in innovative therapy drugs. CellforCure`s industrial platform located in Les Ulis, near Paris is one of the first and largest in Europe for the production of cell and gene therapy drugs. Established as a pharmaceutical company since 2013, CellforCure operates a Contract Development and Manufacturing Organization. The company obtained two Good Manufacturing Practice (GMP) certificates from the French Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) in 2016 for the production of innovative experimental and commercial therapy drugs.

On December 20, 2018 Gritstone Oncology reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to GRANITE-001 for the treatment of colorectal cancer (Press release, Gritstone Oncology, DEC 20, 2018, View Source [SID1234564162]). GRANITE-001 is a personalized immunotherapy containing patient-specific neoantigens identified by Gritstone’s proprietary EDGETM artificial intelligence platform as the most relevant neoantigens to drive a tumor-specific T-cell attack.

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"Colorectal cancer remains a major contributor to cancer deaths and has not yet proved very amenable to first generation immunotherapy," said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone Oncology. "We believe GRANITE-001 has the potential to be a valuable therapeutic option for these patients through its highly personalized design. The ability to leverage tumor markers, or neoantigens, specific to a patient’s own tumor cells in the development of a personalized immunotherapy is regarded as the next frontier of cancer therapy. We look forward to continuing our productive dialogue with the FDA under their Fast Track program as we seek to advance GRANITE-001 expeditiously for the potential benefit of patients."

The FDA grants Fast Track designation to facilitate development and expedite the review of therapies with the potential to treat a serious condition where there is an unmet medical need. A therapeutic that receives Fast Track designation can benefit from early and frequent communication with the agency, in addition to a rolling submission of the marketing application, with the objective of getting important new therapies to patients more quickly.

Ongoing Phase 1/2 Clinical Study
GRANITE-001 in combination with immune checkpoint blockade is being evaluated in a Phase 1/2 clinical study called GO-004 for the treatment of patients with common solid tumors, including metastatic non-small cell lung cancer, microsatellite stable colorectal cancer, gastroesophageal cancer, and bladder cancer. The Phase 1 study includes two parts: in part A patients receive an adenovirus-based prime with escalating doses of an RNA-based boost vaccinations in combination with anti-PD-1 therapy; and in part B patients receive the prime and the boost vaccinations at the selected dose in combination with both anti-PD-1 and anti-CTLA-4 immuno-modulatory antibodies.

About GRANITE-001
GRANITE-001 is Gritstone Oncology’s lead, personalized tumor-specific immunotherapy product candidate. It is engineered to elicit a significant T-cell response (particularly CD8+ cytotoxic T-cells) against mutation-derived tumor-specific neoantigens, or TSNA, identified for each patient through the company’s proprietary EDGE artificial intelligence platform. GRANITE-001 consists of two components, first a priming adenoviral vector followed by monthly boosting with an RNA vector, each containing the same 20 patient-specific TSNA.

On December 20, 2018 CEL-SCI Corporation (NYSE American: CVM) reported financial results for the fiscal year ended September 30, 2018 (Press release, Cel-Sci, DEC 20, 2018, View Source [SID1234532199]). The Company also reported key clinical and corporate developments achieved during fiscal 2018.

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Clinical and Corporate Developments included:

CEL-SCI’s Phase 3 head and neck cancer study continued to follow all 928 patients. The Company is now awaiting final study results. All that remains to be done in this pivotal Phase 3 study, the largest in the world in head and neck cancer, is to continue to track patient survival until it can be determined if the primary endpoint has been met. The primary endpoint of the study, a 10% improvement in overall survival of the Multikine* treatment regimen plus Standard of Care (SOC) vs. SOC alone, will be determined after a total of 298 events have occurred in the two main comparator arms of the study and have been recorded in the study database. These final results could come soon since the last patients were treated in September 2016.
The Phase 3 head and neck cancer study’s Independent Data Monitoring Committee (IDMC) completed two reviews of the data from all 928 patients enrolled in the study in December 2017 and August 2018. The IDMC recommended continuing the study as constituted.
CEL-SCI won its arbitration against the clinical research organization (CRO) inVentiv that ran the Phase 3 head and neck cancer study from 2011-2013. The arbitrator ruled that inVentiv materially breached its contract with CEL-SCI. The arbitrator’s decision vindicated CEL-SCI. This successful conclusion ended a difficult period of time for CEL-SCI, and enabled the Company to move forward with a clean slate.
CEL-SCI started work designed to support the use of its first LEAPS vaccine product candidate, CEL-4000, in human studies for the treatment of rheumatoid arthritis, which will be conducted subject to an Investigational New Drug (IND) application. This work is supported by a $1.5 million grant received from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
CEL-SCI fortified its patent portfolio with three new patents for LEAPS and Multikine. The European Patent Office issued a new Multikine patent titled "A Method for Modulating HLA Class II Tumor Cell Surface Expression With A Cytokine Mixture". This patent addresses Multikine’s mechanism of action to make tumors more visible to the immune system. The U.S. Patent and Trademark Office allowed two new patents for the LEAPS platform technology titled "Method for Inducing an Immune Response and Formulations Thereof" and "Method for Inducing an Immune Response against avian, swine, Spanish, H1N1, H5N9 influenza viruses and formulations". These patents relate to methods for diagnosing, preventing, and treating disease by generating or modulating the immune response through the use of specific peptides.
CEL-SCI raised approximately $21.4 million in gross proceeds during fiscal 2018 through the sale of stock and the exercise of warrants. This left CEL-SCI with about $10.3 million in cash on September 30, 2018.
"We are awaiting a readout of topline results from our Phase 3 head and neck cancer study, the largest of its kind in the world. Results are expected to be available soon. We cannot give a definite time table since we have to wait for 298 events to occur. If Multikine meets it primary endpoint, we believe it may change the way head and neck cancer is treated. We are hopeful that in addition to prolonging life for newly diagnosed patients, Multikine may significantly improve their quality of life by reaping the benefits of immunotherapy before surgery, chemotherapy and radiation therapy degrade their immune systems," stated CEL-SCI CEO, Geert Kersten.

CEL-SCI reported a net loss of $31.84 million in fiscal year 2018 versus a net loss of $14.36 million in fiscal 2017. The increased net loss in 2018 was mainly due to the non-cash derivative loss of approximately $8.6 million recorded during the year ended September 30, 2018 and the approximate $4.8 million non-cash portion of the interest expense. The derivative loss was the result of the change in fair value of the derivative liabilities due to an increase in CEL-SCI’s share price.

The Company’s audited financial statements contained an audit opinion from its independent registered public accounting firm that included an explanatory paragraph related to the Company’s ability to continue as a going concern.

On December 20, 2018 Kleo Pharmaceuticals Inc., a unique immuno-oncology company developing next-generation bispecific compounds designed to emulate or enhance the activity of biologics, reported that its Chief Executive Officer, Douglas J. Manion M.D. FRCP(C), will present at Biotech Showcase 2019 to be held January 6-9, 2019, at the Hilton San Francisco Union Square (Press release, Kleo Pharmaceuticals, DEC 20, 2018, View Source [SID1234532185]).

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Dr. Manion will present an overview of Kleo’s development strategy for its pipeline of small molecule and synthetic peptide compounds that function similar to highly complex biologics, while offering multiple potential advantages. The overview will also outline Kleo’s key value drivers including the three proprietary technology platforms that drive in-house drug development and partnership opportunities, the multiple in-house and collaborative channels through which it is building its immuno-oncology pipeline, and its discovery collaboration with PeptiDream.

Kleo is well-funded to achieve multiple preclinical and early clinical milestones following the November 2018 closing of an oversubscribed $21 million Series B financing to advance its first clinical candidates through IND-enabling studies and into the clinic in 2020.

Details of Kleo’s presentation are as follows:

Event:

Biotech Showcase 2019
Date: Monday, January 7, 2019
Time: 10:45 a.m. (Pacific Time)
Location:Franciscan B Ballroom; Hilton San Francisco Union Square