On January 4, 2018 Rasna Therapeutics, Inc. (OTCQX: RASP), a clinical stage biotechnology company focused on the development of disease-modifying drugs for hematological malignancies, reported follow up Phase II clinical data showing that 4 out of 9 (44%) evaluable AML patients carrying the NPM1 gene mutation treated with actinomycin D ("Act D"), achieved complete remission (CR) (Press release, Rasna Therapeutics, JAN 4, 2018, View Source [SID1234522893]). Treatment with Act D was well-tolerated except that patients experienced oral mucositis as the major toxicity. Rasna Therapeutics has developed a proprietary nanoparticle based formulation of Act D (RASP-101), which is anticipated to maximize efficacy while minimizing oral mucositis. RASP-101 could potentially be a first-in-class modality for treatment of NPM1-mutated acute myeloid leukemia (AML).
NPM1-mutated AML is a specific genetic leukemia entity that accounts for approximately one-third cases of AML in adults. As we reported previously, intravenous treatment of refractory or relapsed NPM1-mutated AML patients with Act D (12.5 µg or 15 µg/day) for 5 consecutive days produced hematological complete response in some of them (Falini et al., N Eng J Med. 373: 12, 2015).

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In a follow-up phase II clinical study (ActD-AML-PG01, EudraCT 2014-000693-18) in refractory/relapse (R/R) AML patients carrying NPM1 gene mutation, treatment with Act D at 15 µg/kg/day for 5 days every 28 days induced CR in 4 out of the 9 evaluable patients (44.4%) with only 1 or 2 cycles of therapy. Three out of the 4 (75%) patients who obtained CR relapsed after 3, 5 and 7 months, respectively. One patient underwent haploidentical allogeneic PBSC transplantation at 3 months after CR achievement and is alive in molecular CR (MRD-negative) after 24 months.

"The precise mechanism of action of Act D in NPM1-mutated AML is still not clearly understood. Follow up data confirms our earlier findings and further support the use of Act D to induce complete hematological remissions with possible long-term molecular responses in NPM1-mutated AML patients. To note, our first previously reported NPM1-mutated AML patient (resistant to hypomethylating therapy) treated with Act D remains in molecular remission at over 3 years since CR achievement," said Dr. Brunangelo Falini, a member of the scientific advisory board of Rasna Therapeutics, Inc.

"We have developed a proprietary formulated Act D (RASP-101), which we anticipate will produce a superior clinical outcome with improved efficacy and safety profile. Emerging data from the multicenter clinical studies will allow us to develop a biomarker strategy to select responsive patients and improve clinical outcome for this unmet clinical need" commented Alessandro Padova, Chairman of Rasna.

About Actinomycin D (Dactinomycin)
Actinomycin D, also known as dactinomycin, a cytotoxic antibiotic produced by Streptomyces parvullus, was approved for medical use in the United States in 1964. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. It is believed to work by blocking RNA synthesis. The drug has been used to treat a number of types of cancers, including Wilms tumor, rhabdomyosarcoma, Ewing’s sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer.

About Dr. Brunangelo Falini, M.D.
Brunangelo Falini is the head of the Institute of Hematology and Hemopoietic Stem Cell Transplantation at the University of Perugia, Perugia, Italy. His research activity has mainly focused on the genetic characterization of lymphomas and leukemias using monoclonal antibodies and, more recently, NGS technologies. He led the research group who discovered NPM1 mutations in AML in 2005 and the BRAF-V600E mutation in hairy cell leukemia in 2011. Both these seminal discoveries have already translated into a better diagnosis and therapy of patients affected by these hematological malignancies. Dr. Falini is the recipient of numerous prestigious prizes, including the "Josè Carreras Award" from EHA (Free EHA Whitepaper) (Barcelona, 2010), the "Leopold Griffuel Prize" from ARC (Paris, 2015) and the "Prize for Excellence in Medicine" from the American-Italian Cancer Foundation (New York, 2017).

On January 4, 2018 SignalRx Pharmaceuticals Inc., a clinical-stage company developing novel small-molecules therapeutics to inhibit key orthogonal and synergistic oncotargets for the treatment of cancer, reported the in silico design and discovery of SRX3225, its first-in-class small-molecule potent inhibitor of three key cancer targets HDAC6, BRD4, and PI3K (Press release, SignalRx, JAN 4, 2018, http://www.ireachcontent.com/news-releases/signalrx-announces-in-silico-design-and-discovery-of-the-first-in-class-hdac6-brd4-pi3k-epigenetic-kinase-inhibitor-srx3225-668070373.html [SID1234527319]).

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SignalRx’s proprietary CRIMP technology platform led to the in silico design and identification of SRX3225 within its triple inhibitor program. SRX3225 is a novel picomolar potent HDAC6 inhibitor with high selectivity over HDAC1, HDAC2 and HDAC3 isoforms (31-35 times selective) and more so against isozymes HDAC4 through HDAC11 (up to 20,000 times selective). In addition, SRX3225 potently inhibits the epigenetic target BRD4-BD1 with >5X selectivity over BRD4-BD2, and it also potently inhibits PI3K alpha and delta isoforms. Importantly, because the design of SRX3225 is achieved in silico using cancer targets’ structural data, it is possible to independently dial in and out each of the three inhibitory components in a small molecule generating dual and single inhibitory chemotypes from SRX3225.

"This is a huge immuno-oncology breakthrough because it creates a synergistic synthetic lethality effect as a result of PI3K and BRD4 and HDAC inhibition delivered with a single molecule. While dual PI3K/BRD4, dual HDAC/PI3K, and dual BRD4/HDAC inhibitors are under investigation, SRX3225 is the only triple HDAC/PI3K/BRD4 inhibitor that we know of" said SignalRx’s scientific advisor and founder Donald L. Durden, MD, PhD. "This new approach of inhibiting three targets simultaneously yields a more complete block of multiple key cancer signaling providing increased lethality coupled with less toxicity than a combination of three single agents. This novel 3-in-1 anticancer drug paves the way for more sophisticated and cost-effective combinations in cancer patients that should block development of resistance resulting in longer duration of benefits in more patients."

"We achieved this milestone by leveraging the experience in multi-targeted inhibitors and discoveries we have made in our advanced BRD4/PI3K program coupled with the knowledge we have acquired on these targets as exemplified in our recent PNAS publication (View Source)" said Dr. Joseph Garlich, Chief Scientific Officer at SignalRx. "Rational combinations of targeted agents in clinical development often face a common detrimental limitation: unwanted additive off-target toxicities from the individual agents used. This leaves no option but to reduce the effective dosages of the agents resulting in less than optimal therapeutic administrations and inefficient treatments. Our approach combines 3 drug mechanisms into one resulting in 1 single agent with a single ADME/safety profile which also simplifies and expedites its development."

SignalRx is interested in partnering discussions to quickly take these novel small molecules through clinical trials together with companion diagnostics for streamlined development and approval.

On January 4, 2018 Illumina, Inc. (NASDAQ: ILMN) and KingMed Diagnostics (SSE: 603882.SS) reported an agreement to jointly develop novel oncology and hereditary disease testing applications utilizing Illumina’s next-generation sequencing (NGS) technology (Press release, Illumina, JAN 4, 2018, View Source [SID1234522917]). The collaboration is a significant step toward China Food and Drug Administration (CFDA) review and approval, and serves as a starting point to deliver precision medicine to patients throughout China.

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Under the agreement, Illumina and KingMed Diagnostics will partner to co-develop an integrated NGS system that provides cost-effective and ready-to-use in-vitro diagnostic (IVD) assays for molecular oncology and hereditary cancer testing. The new system is based on Illumina’s MiniSeq System and related sequencing consumables, integrated with KingMed Diagnostics’ proprietary testing components, which include library preparation kits and analysis software.

The integrated system can reach cancer patients across China via KingMed Diagnostics’ extensive clinical network that serves more than 8,000 Class 2 and Class 3B hospitals.

"KingMed Diagnostics’ motivation is to improve diagnosis and treatment for the more than 4 million new cancer patients identified in China each year. Our mission is to bring state-of-the-art technology to Chinese patients by enhancing their standard of care and improving their outcomes," said Professor Yaoming Liang, Chairman and CEO of KingMed Diagnostics. "Illumina is the ideal collaborator because they have a proven track record of working with multiple domestic companies in China, in addition to being the first company with a U.S. FDA-cleared, next-generation sequencing instrument."

"KingMed Diagnostics is one of the leading independent clinical laboratory service providers in China, and as such, we are excited to partner with them to help customize the MiniSeq System under CFDA requirements for clinical oncology applications," said Garret Hampton, Ph.D., Executive Vice President of Clinical Genomics at Illumina.

"This agreement is a clear demonstration of our commitment to working with broader clinical testing service providers in China who want to develop and commercialize IVDs based on NGS," said Ruilin Zhao, Ph.D., Illumina’s Vice President and General Manager of Greater China. "As we continue to expand our clinical partner networks, we are focused on providing the best healthcare solutions to patients throughout China."

On January 4, 2018 AvantGen reported the successful completion of a first cancer therapeutic antibody discovery program for Tanabe Research Laboratories USA, Inc. (TRL) and the initiation of a second program (Press release, AvantGen, JAN 4, 2018, View Source [SID1234522916]).

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Under the terms of the collaboration, AvantGen is responsible for generating novel antibodies to specified cancer targets using its proprietary human antibody yeast display technology platform. TRL has worldwide rights to develop and commercialize antibodies discovered by AvantGen. AvantGen receives upfront payments and is eligible to receive milestone payments and royalties associated with the development and sale of any products derived from the collaboration.

"AvantGen’s antibody discovery and optimization services have been extensively validated against hundreds of targets primarily through numerous NIH SBIR I and II funded projects. Since the recent introduction of our new, state-of-the-art human antibody discovery and optimization platform, this second project with TRL represents the fifteenth de novo antibody discovery project we have initiated specifically for corporate partners," said Xiaomin Fan, Ph.D., founder and president of AvantGen. "The platform utilizes advantageous technologies, including a robust yeast display system, large natural human antibody database and fully human antibody libraries, for the generation of antibodies to meet challenging design goals for therapeutic, diagnostic and research tool purposes."

"The therapeutic antibody discovery program conducted by AvantGen was highly collaborative and was accomplished faster than expected, without the need to further optimize the antibodies in order to meet TRL’s design goals," said Roland Newman, Ph.D., chief scientific officer for TRL. "We look forward to working together on the second program and others in the future."

On January 4, 2018 CureVac AG, a leading clinical-stage biopharmaceutical company focused on the development of pioneering mRNA therapeutics, and Arcturus Therapeutics Ltd. (NASDAQ:ARCT), an RNA medicines company, reported they have entered into a broad strategic collaboration to jointly discover, develop and commercialize novel messenger RNA (mRNA) therapeutics (Press release, CureVac, JAN 4, 2018, View Source [SID1234522914]).

Under the agreement, the companies will collaborate to develop up to four molecular therapy products for rare diseases using Curevac’s optimized natural mRNA sequence (RNAoptimizer) and Arcturus’s lipid-mediated nucleic acid delivery system (LUNAR). The agreement focuses on developing mRNA therapeutics for enzyme replacement and antibody generation. Development costs will be shared between the companies, with plans to co-commercialize products in the future under a profit sharing arrangement. The first mRNA therapy to be jointly developed and potentially commercialized by the companies will target ornithine transcarbamylase (OTC) deficiency, a genetic disease characterized by the accumulation of ammonia in the blood. The collaboration also grants CureVac access to the full suite of Arcturus’s lipid-mediated delivery intellectual property to enable the development of additional mRNA product candidates.

"This collaboration for up to four products establishes a sound relationship with Arcturus, which we believe is one of the leaders in developing lipid-mediated delivery systems for mRNA molecules," said Ingmar Hoerr, Ph.D., co-founder and CEO of CureVac. "Just as important, we are excited to have secured access to Arcturus’s leading intellectual property rights for future product development in molecular therapies. This partnership combines both companies’ technology platforms with the expertise necessary to develop the next generation of therapeutics based on the considerable potential of mRNA."

"We are thrilled to combine Arcturus’s platform technologies and expertise with CureVac’s recognized capabilities in mRNA construct optimization and GMP manufacturing to co-develop messenger RNA medicines for patients in need," said Joseph Payne, President and CEO of Arcturus. "We believe our collaboration with CureVac has the potential to help reduce costs, mitigate manufacturing risks, and accelerate our timelines for ushering quality mRNA medicines into the clinic."