Aerpio Pharmaceuticals Inc., of San Francisco, and Quantum Leap Healthcare Collaborative said an agreement was reached to evaluate Tie2-activating compound razuprotafib in a new, randomized treatment arm in the I-SPY COVID trial for the treatment of acute respiratory distress syndrome (ARDS) in adults with moderate to severe COVID-19. The goal of I-SPY COVID is to rapidly screen multiple promising agents, in the setting of an adaptive platform trial, for the treatment of critically ill COVID-19 patients to identify agents that will have a high impact on reducing mortality, and the need for as well as duration of, mechanical ventilation. Preclinical models, large human observational studies and human genetic studies have independently arrived at the concept that vascular endothelial receptor Tie2 may play a pivotal role in the defense against microvascular breach in ARDS. Shares of Aerpio (NASDAQ:ARPO) gained 44.5%, or 35 cents, to close May 28 at $1.13.
Alkido Pharma Inc., of New York, said a paper published in the July 2020 issue of Translational Oncology describes results from the company’s research at Wake Forest University showing phospholipid mimetic KPC-34 is active against acute myeloid leukemia (AML) with activated protein kinase C (PKC). In an orthotopic, xenograft model, KPC-34 treatment resulted in a significant increase in survival compared to control animals and those treated with high-dose cytarabine. In a PDX model with activated PKC, there was a significant survival benefit with KPC-34, and at progression, there was attenuation of PKC activation in the resistant cells. In contrast, KPC-34 was ineffective against a syngeneic, orthotopic AML model without activated PKC. However, when cells from that model were forced to express PKC, there were significantly increased sensitivity in vitro and survival benefit in vivo. Those data suggest that KPC-34 is active against AML and that the presence of activated PKC can be a predictive biomarker, the company said.
Cabaletta Bio Inc., of Philadelphia, said it expanded its sponsored research agreement with the University of Pennsylvania to widen the scope of sponsored research to include three additional B-cell-mediated autoimmune diseases.
Chimeron Bio Inc., of Philadelphia, and George Mason University’s National Center for Biodefense and Infectious Diseases agreed to partner on development of a COVID-19 vaccine, to be based on Chimeron’s Chaesar self-amplifying RNA technology and integrating Mason’s expertise and biomedical research laboratory. The Chaesar technology is designed to delivery immunogenic viral genes to elicit rapid and sustained immune response, and its ability to amplify production of viral antigens inside the body is expected to generate a vaccine response at much lower doses vs. traditional mRNA approaches.
CNS Pharmaceuticals AG Inc., of Houston, said it entered a sponsored research agreement with The University of Texas MD Anderson Cancer Center covering potential cancer treatment technologies, including WP-1244, a DNA binding agent that is up to 500 times more potent than the clinically used chemotherapeutic agent daunorubicin in inhibiting tumor cell proliferation.
Daiichi Sankyo Inc., of Tokyo, said it entered a strategic agreement with Morrisville, N.C.-based Syneos Health Inc. to develop cancer therapies. Syneos will provide both strategic and operational solutions for three lead Daiichi Sankyo DXd antibody-drug conjugates: DS-1062, U3-1402 and DS-8201 (known as Enhertu). Cross-functional teams from both companies will share therapeutic expertise and product development insights to shape optimal study designs and create a consistent quality clinical delivery process across a portfolio of studies.
Denali Therapeutics Inc., of South San Francisco, said two papers, published in Science Translational Medicine, describe the company’s Transport Vehicle (TV) technology and illustrate its ability to deliver therapeutic proteins to the brain at levels sufficient for robust effects, and demonstrate the normalization of biomarkers in a disease model of Hunter syndrome. In animal models, antibodies and enzymes engineered with the TV technology have demonstrated more than 20-fold greater brain exposure than similar antibodies and enzymes without this technology. Improved exposure and broad distribution in the brain may enable higher, therapeutically relevant concentrations of product candidates, and thus increase therapeutic efficacy. The company said it expects to start dosing in the first Hunter syndrome patient with DNL-310 in a phase I/II study shortly, and an interim data readout is expected by late in the year.
E-therapeutics plc, of Oxford, U.K., said it has expanded its focus into RNA interference as a therapeutic modality to pursue drug discovery outcomes. The company’s network-driven drug discovery platform leverages a machine learning-enhanced database of more than 15 million small-molecule compounds to perform functional in silico phenotypic screens. In addition, its genome-associated interactions network platform enables the company to determine actionable outcomes from complex genomic datasets.
GNS Healthcare Inc., of Cambridge, Mass., said reported results, published in Leukemia, uncovered transcription factor PHF19 as a novel marker of aggressive multiple myeloma progression in newly diagnosed patients. By identifying PHF19, GNS and collaborators are elucidating potential improvements in clinical trial design and oncologists' treatment decision-making for patients with newly diagnosed multiple myeloma. To validate the marker, collaborators conducted cell line experiments and showed that knockdown of PHF19 leads to decreased proliferation through cell cycle arrest in multiple myeloma. Results from the DREAM competition, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark those against previously published models, generated more than 800 participants and nearly 200 algorithms submitted to the challenge. GNS Healthcare's algorithm was found to be the most accurate in predicting markers of aggressive disease progression, outperforming even those available in commercial tests, the company said.
Kiadis Pharma NV, of Amsterdam, said new data related to its K-NK cell therapy platform will be presented at the International Society of Cell & Gene Therapy virtual meeting. It will show how cytokine pre-activation enhances Kiadis’ PM21-particle-driven NK cell expansion. High-scale expansion of “memory-like” NK cells can be obtained with a combined pre-activation with cytokines followed by expansion with Kiadis’ PM21-platform. NK cells from healthy donor-derived peripheral blood mononuclear cell were stimulated overnight with IL-12, IL-18 and IL-15 and then expanded with PM21 particles. The new methodology resulted in a significantly further increased expansion of NK cells than with PM21 alone. Also, the NK cells that were preactivated produced even larger amounts of IFNγ and were very responsive to activation by K562 tumor cells or cytokines. In addition, receptor expression was similar for both cytokine preactivated NK and PM21 activated NK cells and demonstrated that both are in a highly activated state as compared to IL-2-activated NK cells.
Microbion Corp., of Bozeman, Mont., said it was awarded $17.1 million by Boston’s CARB-X and the Cystic Fibrosis foundation to complete preclinical and phase I studies of pravibismane to treat cystic fibrosis-related pulmonary infections. The award is composed of an initial commitment of up to $6.1 million plus up to $5.4 million more if certain project milestones are met. Pravibismane has a mechanism of action that functions as a microbial bioenergetic inhibitor.
Moderna Inc., of Cambridge, Mass., and contract development and manufacturing organization Cordenpharma signed an amendment to their existing manufacturing agreement to enable Cordenpharma to manufacture large-scale volumes of lipid excipients to be used in the manufacture of Moderna's vaccine candidate (mRNA-1273) against SARS-CoV-2, the virus that causes COVID-19.
Oncimmune Holdings plc, of Nottingham, U.K., said it signed with Roche Group, of Basel, Switzerland, to profile autoantibodies in patient samples collected during cancer immunotherapy trials. The project is designed to explore baseline and on-treatment autoantibody profiles as biomarkers in patients who received cancer immunotherapy. Initial results are to be provided to Roche within three months, with project completion by November.
Oxford Biomedica plc, of Oxford, U.K., said it signed a one-year clinical and commercial supply agreement with Astrazeneca plc, of Cambridge, U.K., for the GMP manufacture of the adenovirus vector-based COVID-19 vaccine candidate AZD-1222, which is in clinical trials in the U.K. Oxford will provide Astrazeneca multiple batches of vaccine, the majority of which are expected to be produced throughout 2020.
Puretech Health plc, of Boston, said it is advancing LYT-100 (deupirfenidone) to treat serious respiratory complications, including inflammation and fibrosis, that persist following the resolution of SARS-CoV-2 infection. LYT-100 employs a multimodal mechanism of action designed to reduce, delay or prevent the lung dysfunction documented in COVID-19 patients, including those who have recovered. The global, randomized, placebo-controlled trial is expected to begin in the third quarter of 2020 and will evaluate LYT-100 in non-critical COVID-19 patients with respiratory complications. Patients will continue treatment for up to three months.
Reflexion Medical Inc., of Hayward., Calif., and Merck and Co. Inc., of Kenilworth, N.J., will collaborate to evaluate the safety and efficacy of Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with BgRT in multiple late-stage cancers, including non-small-cell lung cancer, in two randomized controlled clinical trials. The goal is to establish whether treating multiple tumors with BgRT, an external beam radiotherapy treatment modality in development, is safe and amplifies Keytruda’s therapeutic effect. Reflexion’s X1 machine with BgRT is designed to overcome the technical limitations that restrict radiotherapy delivery to one or two sites of disease and instead allow it to reach multiple sites during the same treatment session, even those sites that move due to breathing or digestion.
Restorbio Inc., of Boston, said it initiated a randomized, double-blind, placebo-controlled trial of RTB-101, an orally administered small-molecule inhibitor of target of rapamycin complex 1, as compared to placebo for COVID-19 prophylaxis in nursing home residents. The study is supported by the company’s phase IIb and phase III trials that suggest RTB-101 could reduce the severity of laboratory-confirmed coronavirus infections. The new study will measure the reduction of severity of laboratory-confirmed COVID-19 in adults 65 and older who reside in a nursing home in which one or more residents or staff have developed laboratory-confirmed COVID-19.
Seelos Therapeutics Inc., of New York, started a preclinical study of SLS-004 in Parkinson’s disease (PD) through an all-in-one lentiviral vector targeting the synuclein alpha (SNCA) gene. Seelos is constructing a bimodular viral system harboring an endogenous alpha-synuclein (α-synuclein) transgene and inducible regulated repressive CRISPR/Cas9-unit to achieve constitutive activation and inducible suppression of PD-related pathologies. Previously, it was shown that enrichment in DNA methylation at intron 1 of the α-synuclein gene SNCA, through SLS-004, facilitated robust and precise repression of SNCA expression, which coincides with rescuing of PD-phenotypes, the company said.
Shanghai Cell Therapy Group Ltd., of Shanghai, signed a six-year research collaborative project with Qi-Long Ying from the University of Southern California. Through the project, sponsored by $3.6 million from the Baize Plan Fund, the Ying laboratory aims to develop conditions for the long-term ex vivo expansion of mouse and human hematopoietic stem and progenitor cells.
The Southwest Research Institute (SwRI), which is using U.S. Department of Defense supercomputers to virtually screen millions of drug compounds to search for and test possible treatment options for COVID-19, was awarded a $1.9 million, one-year contract from the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. to support those efforts. SwRI is working with the supercomputers to rapidly screen potential drug compounds using SwRI’s 3D drug screening software tool, Rhodium. Using supercomputers speeds up the screening process, allowing evaluation of possible therapeutic compounds to increase from 250,000 compounds a day to more than 40 million compounds in just one week, the institute said.
Stallergenes Greer plc, of London, and Anergis SA, of Epalinges, Switzerland, disclosed the results of a joint research study evaluating the effects of second-generation Contiguous Overlapping Peptides (COP) allergen immunotherapy in a therapeutic model of birch pollen allergy, with the aim of shortening allergy immunotherapy administration schemes. COP-Virosomes, COP alone and virosomes alone were compared to a placebo group in an in-house therapeutic model of birch pollen allergy. Recombinant Bet v 1 alone (the major allergen of birch pollen) and natural birch pollen allergen extract were also used as controls in that setting. COP-virosomes were the only synthetic therapy able to fully reverse asthma symptoms as well as lung inflammation (i.e. significant reduction in eosinophils in bronchial fluids), the companies said. Pro-allergenic immune responses also decreased with COP-virosomes therapy.
Synairgen plc, of Southampton, U.K., said recruitment of 100 hospitalized patients in its clinical trial of SNG-001 (inhaled formulation of interferon-beta-1a) in COVID-19 patients has been completed. The study is a double-blind, placebo-controlled trial. The 220-patient trial comprises 100 patients initiated in the hospital and 120 patients initiated in the home setting, the company said.
Tetraphase Pharmaceuticals Inc., of Watertown, Mass., signed an amendment to the merger plan with Acelrx Pharmaceuticals Inc., of Redwood City, Calif., to increase the consideration payable to Tetraphase shareholders. Tetraphase stockholders will receive, for each share of Tetraphase common stock, $0.2434 in cash and 0.7217 of a share of Acelrx common stock, representing approximately $1.43 in up-front per share value, based on the closing price of Acelrx’s common stock as of the close of trading on May 26, in each case subject to downward adjustment in the event that the company’s closing net cash is less than $5 million, and one contingent value right which would entitle the holders to receive potential aggregate payments of up to $14.5 million in cash upon the achievement of certain future Xerava (eravacycline) net sales milestones starting in 2021.
Toshiba Corp., of Tokyo, and a team led by Yozo Nakazawa at the department of pediatrics, Shinshu University, have developed a "tumor-tropic liposome technology" for gene therapy. The technology uses nanosized biodegradable liposomes developed by Toshiba to deliver therapeutic genes to targeted cancer cells and achieves safer gene delivery than viruses used as carriers, the company said. The method can deliver therapeutic genes selectively to tumor cells only. Shinshu and Toshiba presented the technology at the annual meeting of the American Society for Gene & Cell Therapy in Boston.
TSRL Inc., of Ann Arbor, Mich., is continuing development of a transdermal delivery system of Relenza (zanamivir) an inhalation drug product licensed for the treatment and prevention of influenza A and B. The project builds on an initial phase I Small Business Innovation Research (SBIR) award of $600,000 to optimize microneedle formulations for painless administration of zanamivir through the skin. TSRL will receive about $3 million over three years from a phase II SBIR grant.
Vaxxas Inc., of Cambridge, Mass., said Merck & Co. Inc., of Kenilworth, N.J., exercised its option to utilize Vaxxas’ High Density Microarray Patch (HD-MAP) platform for a vaccine candidate. Merck also retains an option to license the HD-MAP technology for two additional vaccines. Under the collaboration agreement, originally signed in 2012, through the exercise of that option Merck gains exclusive worldwide rights to develop and commercialize an undisclosed vaccine using HD-MAP. Vaxxas will receive $12 million in a combination of equity funding and option fees associated with the agreement. In addition, Vaxxas is eligible to receive future option, development and commercial milestone payments. Merck will fund any requested additional research activities conducted by Vaxxas and is responsible for clinical development. In separate news, Vaxxas and Harro Höfliger, a company that specializes in pharmaceutical process engineering and sterile manufacture, said they inked an alliance to develop the world’s first high-throughput, aseptic manufacturing line for production of vaccine products based on Vaxxas’ HD-MAP technology. Single, aseptic-based lines will have a targeted throughput of up to 5 million vaccine products per week. Initial efforts are focused on a pilot line operating in 2021 to be used to support late-stage clinical studies.
Zentalis Pharmaceuticals Inc., of New York, and Tavros Therapeutics Inc., of Durham, N.C., disclosed a collaboration to apply Tavros’ functional genomic discovery platform to develop next-generation targeted small-molecule drug candidates, initially to expand Zentalis’ oncology pipeline. Tavros’ approach allows for an unbiased analysis of intricate cellular signaling pathways to discover novel targets, synthetic lethality pairs, mechanisms to overcome cancer resistance, and unique genetic signatures for clinical trials, the companies said. Terms were not disclosed.