Rocilinostat

WALTHAM, Mass.--(BUSINESS WIRE)-- Regenacy Pharmaceuticals Inc, a clinical-stage biopharmaceutical company developing breakthrough treatments for diabetic and other peripheral neuropathies, announced completion of enrollment of the company’s phase 2 study of ricolinostat, an oral selective histone deacetylase 6 (HDAC6) inhibitor, in painful diabetic peripheral neuropathy (DPN). The company also announced the closing of a $9.3 million Series B financing led by Cobro Ventures with participation from Taiwania Capital Management Corporation, 3E Bioventures Capital, Yonjin Venture, and other undisclosed private investors. Painful DPN is characterized by debilitating symptoms that include pain, aberrant sensation, and loss of motor and sensory function. There is an important medical need for new treatments since available therapies do not address the full spectrum of signs and symptoms and offer only limited relief for many patients. Ricolinostat, and other HDAC6 inhibitors, have shown efficacy in animal models of DPN, chemotherapy-induced peripheral neuropathy (CIPN) and Type 2 Charcot Marie Tooth (CMT) disease, and have demonstrated a promising safety and tolerability profile. The ongoing double-blinded placebo-controlled clinical study, which recently completed enrollment, assesses the efficacy of ricolinostat in patients with painful DPN and other neuropathic symptoms. Initial results are expected to be available later this year. Regenacy plans to use the additional financing from this Series B to continue advancing the ricolinostat clinical development program. “Regenacy is committed to exploring ricolinostat’s unique and differentiating potential to address the underlying pathophysiology of small fiber neuropathies,” said David Michelson, M.D., Regenacy’s Chief Medical Officer. “The compelling data we have seen in preclinical studies indicate ricolinostat’s selective inhibition of HDAC6 may provide meaningful relief to patients suffering from painful DPN and other neuropathies, and we look forward to its continued progression in the clinic.” “We are energized by the ongoing support of our investors who share in our mission to address the underlying causes of peripheral neuropathy,” said John Rocha, Regenacy’s Chief Financial Officer. “This Series B positions Regenacy for continued progress as we uncover the potential of ricolinostat to restore peripheral nerve function.” “We at Regenacy believe that ricolinostat shows first-in-class potential to go beyond symptomatic treatment and instill lasting disease-modifying effects for patients with peripheral neuropathies,” said Simon Jones, Ph.D., Regenacy’s President and Chief Executive Officer. “This Series B financing comes at a pivotal stage in our clinical development, as we continue to evaluate ricolinostat in painful diabetic peripheral neuropathy while simultaneously advancing our joint venture Beijing 3E-Regenacy Pharmaceuticals Co., Ltd. to investigate ricolinostat in patients with chemotherapy-induced peripheral neuropathy (CIPN) in China.” Concurrent with the financing, Todd Kaloudis, Managing Director at Cobro Ventures, has joined Regenacy’s Board of Directors. Additionally, Regenacy announced the appointment of William W. Chin, M.D., SVP of Clinical and Translational Science at Frequency Therapeutics, as Executive Chairman of the Board and Michael Huang, Managing Partner at Taiwania Capital, as Vice-Chairman, effective immediately. Mr. Huang has served on Regenacy’s Board since 2020, and Dr. Chin has served since 2018 and is Chairman of Regenacy’s Scientific Advisory Board. About Ricolinostat Ricolinostat, an oral, selective histone deacetylase 6 (HDAC6) inhibitor, has the potential to become the first-in-class treatment that reverses the underlying peripheral neuropathy, thereby relieving pain, numbness, motor function loss, and all other symptoms of the disease. Ricolinostat restores nerve function by inhibiting HDAC6, which reestablishes the transport function of microtubules in the axon of the nerve cell. A functioning microtubule transport system is the key to restoring nerve function because nerves rely on this network to supply the energy and nutrients necessary to maintain the nerve signaling in the ends of the nerves in the skin and muscles of the feet and hands. When this transport is disrupted by a disease like diabetes or neurotoxic drugs used in chemotherapy, nerve cells can malfunction and send random signals (pain, tingling, muscle spasms) or no signal at all (numbness, paralysis). Multiple preclinical animal models have demonstrated that HDAC6 inhibition restores nerve fibers, leading to the reversal of both pain and numbness in peripheral and other neuropathies, such as diabetic peripheral neuropathy (DPN), chemotherapy-induced peripheral neuropathy (CIPN) and Charcot-Marie-Tooth disease Type 2, an orphan-designated disease. About Regenacy Regenacy Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company regenerating biological function by protein acetylation for the treatment of diabetic and other peripheral neuropathies and other chronic conditions. The company’s selective inhibition technology provides superior safety profiles and potential enhanced efficacy compared to non-selective HDAC inhibitors. Regenacy selectively inhibits histone deacetylase 6 (HDAC6) to restore normal intracellular protein and organelle transport in peripheral neuropathies, and also has a portfolio of selective HDACs 1 and 2 inhibitors that have potential to treat major blood diseases such as leukemia, sickle cell disease, β-thalassemia, and cognitive dysfunction in neurological disorders.

NEW YORK, Jan. 11, 2021 /PRNewswire/ -- DarwinHealth, Inc., a New York-based biotechnology and cancer drug discovery company announces the January 11, 2021 online publication in Cell of a landmark paper, "A Modular Master Regulator Landscape Controls Cancer Transcriptional Identity,"1,2 in which scientists from Columbia University and DarwinHealth apply the VIPER (Virtual Inference of Protein activity by Enriched Regulon) analysis algorithm to identify recurrent regulatory networks—"tumor checkpoints"—operative across the pancancer subtype continuum. This research paper, with lead author Dr. Evan Paull, from the Department of Systems Biology at Columbia University, in conjunction with DarwinHealth Co-Founder, Professor Andrea Califano and Chief Scientific Officer, Dr. Mariano Alvarez and other investigators, presents results and analyses, using a novel Multi-Omics Master-Regulator Analysis framework (MOMA), that validates the foundational paradigm informing DarwinHealth technologies. The study, funded by the U.S. National Institutes of Health and the Instituto de Salud Carlos III/Ministerio de Asuntos Economicos y Transformacion Digital (Spain), demonstrates that different genetic alterations in individual patients within the same tumor subtype induce aberrant activation of the same Master Regulator proteins, which maintain the subtype's transcriptional identity. Moreover, it shows that Master Regulators operate within small, hyperconnected modules (Master Regulator Blocks [MRBs]) that mechanistically control key cancer hallmarks necessary for the survival of the cancer cell. The results reported in Cell provide one of the most comprehensive confirmations to date of the value of proprietary, network-based approaches for the identification of therapeutic targets in cancer using VIPER technology. The latter has been exclusively licensed, for commercial use, to DarwinHealth by Columbia University. The Cell publication concludes that, "Taken together, these data suggest that MRBs may provide complementary 'molecular recipes' for implementing the same cancer hallmarks in different tumor contexts." "These data support the Oncotecture Hypothesis, which suggests that a much larger and finer grain mutational repertoire than previously suspected may be responsible for inducing aberrant MR activity and implementing transcriptional tumor identities," explains Dr. Califano. "The results presented by this multi-disciplinary team also confirm that Tumor Checkpoint-based Master Regulators implement regulatory bottlenecks in cancer that are responsible for canalizing the effect of multiple functional mutations." He adds that, "Importantly, the Tumor Checkpoints that define each subtype can thus be deconstructed into highly specific combinations of a handful of activated and inactivated Master Regulator-Blocks—specifically, 24 identified in this study. The MRBs can potentially regulate complementary genetic programs required to implement and maintain a tumor cell's transcriptional identity, which undergirds key aspects of cancer cell behavior and determines susceptibility to specific drugs and therapeutic interventions." The study provides a data-driven roadmap for identifying potential therapeutic targets that may benefit a large subset of cancer patients within each one of 112 tumor subtypes, independent of their mutational state, characterized by the analysis. Accordingly, the authors note that, "Consistent with the notion that transcriptional cell states have emerged as more accurate predictors of drug-sensitivity compared to genetics, this suggests that MR-based analyses may produce a more tractable landscape of potential therapeutic targets than what could be achieved by genetic-based approaches." These research findings and planned follow-up studies are likely to change the trajectory of classification schemes for cancer and evolving approaches to precision-based drug discovery in a number of important ways. The methodologies and results reported in Cell introduce to the cancer research and clinical community an entirely new approach for taxonomizing cancer subtypes—essentially, categorizing them according to the composition of downstream regulatory bottlenecks with unique compositions of MRBs representing targetable tumor dependencies, independent of canonical mutational signatures. In fact, ongoing studies suggest these MR-based, tumor checkpoints are more reliable off-on switches for cancer cell governance than mutations themselves. Accordingly, this novel, data-driven taxonomization of molecular species (i.e., MR proteins comprising tumor checkpoints) responsible for cancer cell behavior—and susceptibility to therapeutic targeting—represents a paradigmatic shift opening up multiple avenues of inquiry and applications that have translational impact at the front lines of clinical care for cancer patients. Dr. Gideon Bosker, DarwinHealth CEO, notes, "The new molecular classification reported in Cell sets the stage for identifying and testing drugs that can induce a state of 'regulatory network contraception,' that is, disable or disrupt formation of checkpoint-governed programs that maintain and perpetuate the cancer cell state." Importantly, the identification of Master Regulators has been made possible by the VIPER technology, developed by Califano and Alvarez at Columbia and licensed exclusively to DarwinHealth. VIPER allows precise measurement of protein activity from inexpensive and easily-accessible gene expression profiles—as measured by mRNA sequencing. Much like thermostats maintain a constant room temperature, the VIPER-inferred Master Regulators coalesce into complex auto-regulated modules—the tumor checkpoints—that are necessary and sufficient to maintain a consistently programmed malignant state of the cancer cell over time. "The coordinated activity of Master Regulator proteins comprising the tumor checkpoint activates key hallmark programs needed by the cancer cell," explains Dr. Alvarez, DarwinHealth CSO. "Among them are those controlling unchecked proliferation, migration, and metastatic progression—while suppressing other hallmark functions controlling programmed cell death (or apoptosis) and immune system detection; as well as others, which would otherwise prevent tumor formation. Essentially, by channeling genetic and mutational information into a discrete downstream regulatory nexus, the Master Regulators in a tumor checkpoint initiate and maintain the biological and behavioral hallmarks of a cancer cell." "At DarwinHealth, we use the full spectrum of proprietary, patented VIPER-based technologies developed by our scientists and co-founders to accurately and reproducibly quantify the activity of Master Regulators," explained Dr. Bosker. "From an actionable and real world precision oncology perspective, we have developed specific VIPER-based diagnostic tests, including DarwinOncoTreat and DarwinOncoTarget, to pinpoint drugs that can invert the activity of an entire tumor checkpoint or of specific master regulators. These algorithms have received New York and California CLIA certification and are being used clinically, including in several ongoing clinical trials." The first clinical trial based on this technology, which employed the combination of the HDAC6 inhibitor ricolinostat and NAB-paclitaxel, has shown virtually 100% accuracy in the prediction of responders and non-responders as reported in a recent manuscript currently under review and available on MedRxiv (medRxiv 2020.04.23.20066928). DarwinHealth's oncotecture-based, "digging deeper than genes" discovery framework and associated technologies described in the Cell paper will continue to exploit a complementary combination of experimental and computation-based, inferential methods to identify novel cancer targets, effective drugs and biomarkers on a fully mechanistic, rather than empirical basis, in line with the strategies reported Cell. In addition, the company's drug and novel cancer target discovery programs, including the DarwinOncoMarker, Compound-2-Clinic (C2C), and novel cancer target initiative (NCTI) platforms allow its scientific teams, working either independently or in collaboration with biopharmaceutical partners, to target cancer at its most vulnerable and stable spots; more specifically, at the regulatory interfaces implemented by tumor checkpoints. These DarwinHealth technologies and methods, already widely published in leading scientific and medical journals, are currently being evaluated in numerous clinical trials across the globe. By using Master Regulator-based analyses and leveraging their capacity for dissecting more actionable therapeutic targets—and by extension, discovering more effective drugs—than could be achieved by genetic-based approaches alone, these validated approaches are expected to address the precision deficit shortfalls associated with more traditional, mutation-centric approaches to precision oncology, many of which have failed to fully deliver on their initial promise. About DarwinHealth DarwinHealth: Precision Therapeutics for Cancer Medicine is a "frontiers of cancer," biotechnology-focused company, co-founded by CEO Gideon Bosker, MD, and Professor Andrea Califano, Clyde and Helen Wu Professor of Chemical Systems Biology and Chair, Department of Systems Biology at Columbia University. The company's technology was developed by the Califano lab over the past 15 years and is exclusively licensed from Columbia University. DarwinHealth utilizes proprietary, systems biology algorithms to match virtually every cancer patient with the drugs and drug combinations that are most likely to produce a successful treatment outcome. "Conversely, these same algorithms also can prioritize investigational drugs and compound combinations of unknown potential against a full spectrum of human malignancies, as well as novel cancer targets," explained Dr. Bosker, "which make them invaluable for pharmaceutical companies seeking to both optimize their compound pipelines and discover mechanistically actionable, novel cancer targets and compound-tumor alignments." DarwinHealth's mission statement is to deploy novel technologies rooted in systems biology to improve clinical outcomes of cancer treatment. Its core technology, the VIPER algorithm, can identify tightly knit modules of master regulator proteins that represent a new class of actionable therapeutic targets in cancer. The methodology is applied along two complementary axes: First, DarwinHealth's technologies support the systematic identification and validation of druggable targets at a more foundational, deep state of the cancer cell's regulatory logic so we and our scientific partners can exploit next generation actionability based on fundamental and more universal tumor dependencies and mechanisms. Second, from a drug development and discovery perspective, the same technologies are capable of identifying potentially druggable novel targets based on master regulators, and upstream modulators of those targets. This is where the DarwinHealth oncotectural approach, with its emphasis on elucidating and targeting tumor checkpoints, provides its most important solutions and repositioning roadmaps for advancing precision-focused cancer drug discovery and therapeutics. The proprietary, precision medicine-based methods employed by DarwinHealth are supported by a deep body of scientific literature authored by its scientific leadership, including DarwinHealth CSO, Mariano Alvarez, PhD, who co-developed the company's critical computational infrastructure. These proprietary strategies leverage the ability to reverse-engineer and analyze the genome-wide regulatory and signaling logic of the cancer cell, by integrating data from in silico, in vitro, and in vivo assays. This provides a fully integrated drug characterization and discovery platform designed to elucidate, accelerate, and validate precise developmental trajectories for pharmaceutical assets, so their full clinical and commercial potential can be realized. For more information, please visit: . 1Cell 184, 1–18, January 21, 2021 (print version) 2Cell (online pub, January 11, 2021),