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Rocket Pharmaceuticals and Inotek Pharmaceuticals Complete Merger Transaction

On January 4, 2017 Rocket Pharmaceuticals, Ltd., a leading U.S.-based multi-platform gene therapy company addressing challenging rare diseases, reported the completion of its merger with Inotek Pharmaceuticals Corporation ("Inotek") (Press release, Rocket Pharmaceuticals, JAN 4, 2018, View Source [SID1234522921]). The combined company ("Company") will be named Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) ("Rocket") and will focus on advancing a pipeline of gene therapy programs targeting rare and undertreated diseases. Rocket’s common stock will be listed on the NASDAQ Global Market under the symbol "RCKT" and is expected to be begin trading on January 5, 2018. Rocket is based in New York City and led by President and Chief Executive Officer Gaurav Shah, M.D., who previously was a Global Program Head in the Cell & Gene Therapies Unit at Novartis.

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"The support for this transaction by both Inotek and Rocket shareholders was evident today, underscoring support for our long-term growth strategy to become a fully-integrated, multi-platform gene therapy company"

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"The support for this transaction by both Inotek and Rocket shareholders was evident today, underscoring support for our long-term growth strategy to become a fully-integrated, multi-platform gene therapy company," said Dr. Shah. "The closing of this merger provides immediate value to grow our operations, execute on our clinical development goals, and expand our in-house manufacturing and analytics capabilities. As we enter this next stage of growth as a publicly traded company, we are focused on driving Company value by bringing our current pipeline of five programs to major value inflection points as rapidly as possible, and achieving first mover advantage in these markets."

Rocket’s Pipeline

Rocket utilizes a multi-platform development approach that leverages the well-established lentiviral vector (LVV) and adeno-associated viral vector (AAV) gene delivery methods and is initially targeting devastating rare diseases in children that lead to early mortality in the absence of bone marrow transplant or other invasive procedures.

The Company’s lead program, a Phase 1/2 LVV-based gene therapy for Fanconi Anemia (FA), is currently in clinical trials with academic partners in the U.S. and Europe. FA causes genetic instability due to mutations in DNA repair genes resulting in early bone marrow failure and malignancy. Early results in FA patients have demonstrated clinical engraftment of ex vivo-transduced autologous hematopoietic stem cells (HSCs). The proportion of gene-corrected cells increases over time, confirming the selective advantage of gene-corrected cells in the bone marrow without requiring conditioning (i.e. destruction of bone marrow prior to transplant). Functional correction and clinical proof of concept have also been observed. Both blood and marrow cells demonstrate resistance to DNA-damaging agents (sensitivity to DNA-damaging agents is a diagnostic feature of FA). Patients demonstrated stable or improving blood cell counts during the months following treatment despite decreases noted during the months and years preceding gene therapy. Additional patient data are expected in 2018, with a registration study anticipated to start in 2019.

Three additional LVV-based programs are currently in preclinical development and target Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD) and Infantile Malignant Osteopetrosis (IMO). The LAD-I program is expected to advance into the clinic in 2018, with the PKD and IMO programs to follow in 2019.

An undisclosed AAV-based gene therapy program is expected to enter the clinic in the next year and has demonstrated encouraging histological correction of the disease phenotype. This program targets a monogenic pediatric disease with early mortality and represents the first gene therapy being developed for this large class of indications.

Rocket’s Management

The combined Company’s executive management team will be led by Dr. Shah and will consist of: Jonathan Schwartz, M.D., Chief Medical Officer, who led several biologics approvals as Vice President of Clinical Development at ImClone Systems/Eli Lilly and Company; Kinnari Patel, Pharm.D., MBA, newly appointed Chief Operating Officer, who led regulatory filings for six rare disease agents as well as for Opdivo while at Bristol-Myers Squibb; and Brian Batchelder, MBA, Vice President of Finance, who previously served as Chief Financial Officer of ImClone Systems, a subsidiary of Eli Lilly and Company.

In addition, Rocket appointed Claudine Prowse, Ph.D., as Head of Corporate Development and Investor Relations Officer. Previously, she was Head of Strategy at Inotek, where she was integral to the merger transaction with Rocket Pharmaceuticals, Ltd. Prior to that, she was Vice President of Investor Relations at Biogen.

About the Merger

Prior to the closing of the merger, Inotek effected a 1 for 4 reverse split of its common stock. Following the reverse stock split and closing of the merger, there will be approximately 33.1 million shares of the combined company’s common stock outstanding with prior Rocket shareholders owning approximately 79.4% and prior Inotek shareholders owning approximately 20.6%. Based on the reverse stock split, the conversion rate of the combined Company’s $52.0 million of 5.75% Convertible Senior Notes due 2021 will automatically be adjusted from 124.7505 shares of common stock per $1,000 principal amount of the notes to 31.1876 shares of common stock per $1,000 principal amount of the notes. Cash, cash equivalents and short-term investments for the combined Company at closing were approximately $117.2 million.

Rasna Therapeutics, Inc., Announces Follow Up Phase II Clinical Data Confirming Efficacy of Actinomycin D in Patients with NPM1-mutated Acute Myeloid Leukemia

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).

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).

SignalRx Announces In Silico Design And Discovery Of The First-In-Class HDAC6-BRD4-PI3K Epigenetic Kinase Inhibitor SRX3225

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]).

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.

Illumina and KingMed Diagnostics Partner to Develop Next-Generation Sequencing Technology for Chinese FDA 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.

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."

AVANTGEN AND TANABE RESEARCH LABORATORIES EXPAND COLLABORATION FOR THERAPEUTIC ANTIBODY DISCOVERY

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]).

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."