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Aravive Biologics Completes Phase 1 Trial of Novel GAS6-AXL Pathway Inhibitor, AVB-S6-500

On July 10, 2018 Aravive Biologics, Inc. reported that the company has completed both the single ascending dose and repeat dose portions of its Phase 1 study of AVB-S6-500 in healthy volunteers (Press release, Aravive Biologics, JUL 10, 2018, View Source [SID1234528276]).

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The study met the safety and tolerability endpoints for the trial. As previously announced, the study also demonstrated clinical proof-of-mechanism for AVB-S6-500 in neutralizing GAS6, based on analysis of the single ascending dose portion of the study which demonstrated a dose-dependent decrease in measurable, circulating free GAS6 in serum. Aravive plans to submit full results of the study for potential presentation at a major medical meeting later in 2018. Also during the second half of 2018, the company expects to initiate the Phase 1b portion of a Phase 1b/Phase 2 trial combining AVB-S6-500 with standard-of care-therapies in patients with platinum-resistant ovarian cancer.

Elevated GAS6 levels have been associated with poor prognosis in cancer. As a decoy molecule, AVB-S6-500 has been shown to neutralize GAS6 activity by binding to that molecule with very high affinity. In doing so, AVB-S6-500 selectively inhibits triggering of the GAS6-AXL signaling pathway. In preclinical studies, GAS6-AXL inhibition has shown activity, whether achieved by a single agent (including AVB-S6-500) or through combinations of a variety of anticancer therapies including radiation therapy, immuno-oncology agents, and drugs that affect DNA replication and repair. Inhibition of the GAS6-AXL pathway has also shown potential as a strategy for the treatment of certain fibrotic diseases.

"We are pleased with the positive outcome of this first study of AVB-S6-500 in humans. The results not only demonstrated initial safety and tolerability for this therapeutic candidate but clearly showed a dose-related reduction of circulating free GAS6, a measurement that we anticipate will be highly useful as a biomarker of drug activity in future clinical studies," said Gail McIntyre Ph.D., DABT, Senior Vice President of R&D at Aravive. "We look forward to our anticipated initiation of the Phase 1b portion of our planned Phase 1b/Phase 2 studies in ovarian cancer during the second half of this year, which are designed to evaluate the anti-cancer effects of lowering of GAS6 in patients with ovarian cancer."

Syros to Host Key Opinion Leader Symposium on Acute Myeloid Leukemia and Myelodysplastic Syndrome on July 17, 2018

On July 10, 2018 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company pioneering the discovery and development of medicines to control the expression of genes, reported that it will host a key opinion leader (KOL) breakfast symposium focused on the unmet need, treatment landscape and opportunity for new combination approaches in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) from 8:30-10:30 a.m. ET on Tuesday, July 17, 2018 in New York City (Press release, Syros Pharmaceuticals, JUL 10, 2018, View Source [SID1234527702]). Syros is currently evaluating SY-1425, its first-in-class, selective retinoic acid receptor alpha (RARα) agonist, in a Phase 2 clinical trial in combination with standard-of-care and targeted therapies in genomically defined subsets of AML and MDS patients.

The event will feature presentations from Rachel J. Cook, M.D., M.S., Assistant Professor of Medicine and Site Director for Acute Leukemia at the Knight Cancer Institute, Oregon Health and Science University and Eytan M. Stein, M.D., Assistant Professor of Medicine; Leukemia Service, Department of Medicine at Memorial Sloan Kettering Cancer Center. Additionally, members of Syros’ management will provide an overview of SY-1425 and review preclinical and clinical data supporting its combination strategy with SY-1425.

A live webcast of the event will be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 30 days following each presentation.

Aptose Biosciences and CrystalGenomics Announce Issuance of Japanese Patent for CG-806

On July 10, 2018 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ:APTO) (TSX:APS), reported that the Japan Patent Office has issued Japanese Patent No. 6325573 for CG-806 (Press release, Aptose Biosciences, JUL 10, 2018, View Source;p=RssLanding&cat=news&id=2357553 [SID1234527629]). The granted patent claims various compounds, including the CG-806 compound, pharmaceutical compositions comprising the CG-806 compound, and uses for the treatment of various diseases, such as cancer. The patent is expected to provide protection until the end of 2033.

"This newly issued patent extends the CG-806 patent protection into an important market and is a welcome addition to the US patent that was issued last year," stated Dr. William G. Rice, Chairman, President and Chief Executive Officer of Aptose. "As noted previously, we plan to continue expansion of the patent portfolio through additional findings and applications."

About CG-806

CG-806 is an oral, first-in-class pan-FLT3/pan-BTK multi-kinase inhibitor. This small molecule demonstrates potent inhibition of wild type and mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), eliminates acute myeloid leukemia (AML) tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with AML. Likewise, CG-806 demonstrates potent, non-covalent inhibition of the wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinase pathways operative in B cell malignancies, suggesting CG-806 may be developed for various B cell malignancy patients (including CLL, MCL, DLBCL and others) that are resistant/refractory/intolerant to covalent BTK inhibitors.

Transgene and Tasly Biopharmaceuticals Conclude Strategic Agreements for the Rights of Transgene’s Virus-Based Immunotherapies TG6002 and TG1050 in Greater China

On July 10, 2018 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapies against cancers and infectious diseases, signed a series of agreements with Tasly Biopharmaceuticals Co., Ltd. ("Tasly Biopharmaceuticals") involving T601 and T101, two immunotherapeutics developed by the Transgene-Tasly joint venture in China (Press release, Transgene, JUL 10, 2018, View Source [SID1234527652]). These products incorporate Transgene’s TG6002 and TG1050 technologies, respectively. As a result of these agreements Transgene will receive shares in Tasly Biopharmaceuticals valued at $48 million. These agreements are designed to further deliver the potential of Transgene’s virus-based technologies in China.

Philippe Archinard, Chairman and Chief Executive Officer of Transgene, added: "We are delighted to have signed these strategic agreements that create value for Transgene through our share ownership in Tasly Biopharmaceuticals and demonstrate the significant potential of the oncolytic virus T601 and therapeutic vaccine T101 in China. As a long-standing partner of the Tasly group, Transgene will remain involved in the further development of these products in China. We look forward to the first readout of the ongoing Phase 1 trial evaluating T101 against chronic hepatitis B, which is expected early 2019. In addition, a Phase 1 trial with the oncolytic virus T601 in China is actively being prepared."

Kaijin Yan, Holding Group Executive Chairman of the Board of Tasly Pharmaceuticals, commented: "Our mission is to become a world-leading biotechnology company, dedicated to continuously offer high-quality and affordable drugs to patients. These new strategic agreements with Transgene provide us with the full development and commercial rights to T601 (through 100% ownership of the joint venture) and T101 in Greater China and will allow us to build a broad innovative product portfolio. We are very happy to welcome Transgene as a key supportive shareholder of Tasly Biopharmaceuticals."

Structure of the transactions
Transgene is transferring its 50% share of the current Transgene-Tasly joint venture (Transgene Tasly (Tianjin) BioPharmaceutical Co., Ltd.) to Tasly Biopharmaceuticals, making it the 100% owner of the joint venture entity and the greater China patent rights to T601.
In parallel, Transgene is assigning the T101 patent rights in Greater China, to which the joint venture held an option, directly to Tasly Biopharmaceuticals.
As a result of these transactions, which are subject to customary closing conditions including completion of the administrative transfer of the assets contributed by Transgene to Tasly Biopharmaceuticals, Tasly Biopharmaceuticals will control all research, development and commercial rights to T601 and T101 in Greater China. In return, Transgene is receiving an aggregate of $48 million in newly created Tasly Biopharmaceuticals shares, representing 2.53% of the Tasly Biopharmaceuticals capital post completion of the Tasly Biopharmaceuticals’s pre-IPO investment round which priced simultaneously with Transgene’s transactions. Tasly Biopharmaceuticals has announced its intention to list its shares on the Hong Kong Stock Exchange.

Lazard and the Adamas law firm advised Transgene on the transaction.

A conference call in English is scheduled on July 10th at 4:00 p.m. CET.

Advaxis Provides Update on MAA Filing and ADXS-HOT Program

On July 10, 2018 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported a clinical update, as follows (Press release, Advaxis, JUL 10, 2018, View Source [SID1234527648]):

Plans to withdraw its Conditional Marketing Authorization Application (MAA) in the European Union for axalimogene filolisbac to treat metastatic cervical cancer in patients who progress beyond first-line therapy

Submission of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to study its first ADXS-HOT drug candidate for the treatment of non-small cell lung cancer (NSCLC)

Selection of prostate cancer as the second cancer type within its ADXS-HOT program to move towards the clinic, with an IND filing anticipated within the next six months

Advaxis’ regulatory action in Europe is based on European Medicines Agency (EMA) feedback following its initial review indicating the application will likely need additional data to support a conditional approval. The February 2018 submission included data from the Phase 2 GOG-0265 study in 50 patients, which showed a 12-month overall survival rate (primary efficacy endpoint) of 38% (n=19/50) in women with persistent, recurrent or metastatic carcinoma of the cervix, representing a 55% improvement over a model-predicted 12-month overall survival rate of 24.5%. As more than half of the women treated in this study had received multiple prior lines of therapy including with bevacizumab treatment, the 38% 12-month overall survival rate was unprecedented when compared against historical data.

The Company continues to believe that the results from the GOG-0265 study are clinically meaningful and provide proof-of-concept that axalimogene filolisbac demonstrated clinical activity in metastatic cervical cancer. The withdrawal of this application does not impact the ongoing clinical trials of axalimogene filolisbac. As previously communicated, Advaxis is actively seeking a partner to support the late-stage cervical cancer program.

The Company also announced that it has submitted an IND with the FDA to study its first product candidate from the ADXS-HOT program, ADXS-503, for the treatment of NSCLC. Upon allowance of the IND for ADXS-503, the Company plans to initiate an open-label, Phase 1/2 clinical trial. Further details of the study design will be provided after the IND is allowed. Advaxis expects the first patient will be dosed by the end of 2018. Additionally, Advaxis anticipates submitting a second IND from the ADXS-HOT program within the next six months, for its drug candidate referred to as ADXS-504, for the treatment of prostate cancer.

"We are pleased to submit the ADXS-503 IND and look forward to advancing our ADXS-HOT NSCLC drug candidate into the clinic. Our ADXS-HOT program leverages both the benefits of our Lm technology platform, which has shown clinical activity in earlier generation drug candidates, and the use of neoantigen targets. We believe that neoantigen-based treatments have the potential to transform cancer care, and the ADXS-HOT program allows us to develop cancer-type specific therapies across a broad range of tumor types," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "With our announcement today of plans for a second IND submission for an ADXS-HOT construct in prostate cancer, we feel confident we can reach proof-of-concept for these off-the-shelf therapeutics in a relatively rapid and cost-effective manner."

Advaxis affirms plans to submit a total of four INDs for drug candidates from its ADXS-HOT program by the end of calendar year 2019, resulting in Phase 1/2 studies evaluating safety, immune responses and preliminary clinical activity of four different constructs addressing four different tumor types. Beyond NSCLC and prostate cancer, the next two ADXS-HOT product candidates will be selected from breast, colorectal, bladder, ovarian and head and neck cancers.

About ADXS-HOT
ADXS-HOT is a program that leverages the Company’s proprietary Lm technology to target hotspot mutations that commonly occur in specific cancer types. ADXS-HOT drug candidates are designed to target acquired shared or "public" mutations in tumor driver genes along with other cancer-testes and oncofetal tumor-associated antigens that also commonly occur in specific cancer types. Although ADXS-HOT drug candidates have not yet been tested in patients, each product candidate has been designed to potentially treat all patients with a specific cancer type, without the need for pre-treatment biomarker testing, biopsy, DNA sequencing or diagnostic testing.