PITTSBURGH and CAMBRIDGE, Mass., May 12, 2022 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (Nasdaq: NBSE) (NeuBase or the Company), a biotechnology platform company Drugging the Genome to address disease at the base level using a new class of precision genetic medicines, today reported its financial results for the three-month period ended March 31, 2022, and other recent developments.

We are pleased with the progress being made across our development pipeline of therapeutic programs to treat DM1, HD, and KRAS-driven cancers. The new data weve announced to date this year have further validated the use of our PATrOLplatform to design novel genetic medicines that target and rescue gene dysfunctions, with the potential for clinically impactful outcomes in both rare and common diseases, said Dietrich A. Stephan, Ph.D., Founder, Chief Executive Officer, and Chairman of NeuBase. We continue to execute the development strategy for our DM1 program, which includes a series of IND-enabling studies scheduled to report data throughout CY2022. Last quarter, we presented pharmacodynamic data that illustrated a single intravenous (IV) dose or multiple subcutaneous (SC) doses of our DM1 development candidate resolves the genetic defect and myotonia in skeletal muscle of the gold-standard mouse model of the disease. Building off these results, we plan on announcing at ASGCT additional pharmacokinetic (PK) data, which will illustrate the exposure levels of our development candidate when administered via systemic administration in skeletal muscles, heart, and brain, tissues that are affected in DM1. We expect these data to support further advancement of our lead candidate for DM1 and validate a differentiated whole-body solution for this disease. Considering this progress, we believe the submission of an IND application to the FDA is on track for the fourth quarter of CY2022.

Second Quarter of Fiscal Year 2022 and Recent Operating Highlights

Financial Results for the Second Fiscal Quarter Ended March 31, 2022

Financial Results for the Six-Month Period Ended March 31, 2022

About NeuBase TherapeuticsNeuBase is accelerating the genetic revolution by developing a new class of precision genetic medicines that Drug the Genome. The Companys therapies are built on a proprietary platform called PATrOL that encompasses a novel peptide-nucleic acid antisense oligonucleobase technology combined with a novel delivery shuttle that overcome many of the hurdles to selective mutation engagement, repeat dosing, and systemic delivery of genetic medicines. With an initial focus on silencing disease-causing mutations in debilitating neurological, neuromuscular, and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions, who currently have limited to no treatment options. To learn more, visit http://www.neubasetherapeutics.com.

Use of Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by use of words such as "will," "would," "anticipate," "expect," "believe," "designed," "plan," or "intend," the negative of these terms, and similar references to future periods. These forward-looking statements include, among others, those related to the plan to provide updates on the Company's development pipeline, in particular the DM1 program, at the ASGCT 25th Annual Meeting, the potential and prospects of the Companys proprietary PATrOL platform and DM1 program, the Companys expectation that it will submit an IND application for the DM1 program to the U.S. Food and Drug Administration in the fourth quarter of CY2022, our expectations to initiate scale-up and toxicology activities for development of a systemically administered allele-selective NT-0100 program to treat HD in CY2022, the potential of our therapeutic program for HD and the potential for our PATrOL-enabled compounds to silence activating KRAS point mutations in vivo to inhibit protein production. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the U.S. Securities and Exchange Commission, may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Company's current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the Company's plans to develop and commercialize its product candidates; the timing of initiation of the Company's planned clinical trials; the risks that prior data will not be replicated in future studies; the timing of any planned investigational new drug application or new drug application; the Company's plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the Company's product candidates; the Company's commercialization, marketing and manufacturing capabilities and strategy; global health conditions, including the impact of COVID-19; the Company's ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors contained in our filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

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NeuBase Therapeutics Reports Business Update and Financial Results for the Second Quarter of Fiscal Year 2022 - GlobeNewswire

This discovery validates siderophore secretion as a drug target in tuberculosis and reveals a new mechanism for putative drugs. Many tuberculosis bacteria are highly resistant to multiple antibiotics.

Michael Niederweis, left, and Lei ZhangLei Zhang, Ph.D., and Michael Niederweis, Ph.D., of the University of Alabama at Birmingham have made what they call a major step in understanding how Mycobacterium tuberculosis acquires iron from its human host a process essential for the pathogenesis of this bacterium. Tuberculosis kills more than 1 million people each year, but without iron, M. tuberculosis cannot grow.

In general, bacteria acquire iron in a well-understood manner. They produce molecules called siderophores, which is Greek for iron carrier, and they use molecular pumps to excrete the siderophores out through the inner and outer membranes. The siderophores have the ability to bind iron very tightly. Then these iron-clutching siderophores are transported back into the bacteria. Inside, the iron is released for use in essential enzymes.

However, the Mycobacteriaceae family which includes the microbial pathogens for tuberculosis and leprosy differ greatly from bacteria like E. coli, where the machinery involved in siderophore transport has been heavily studied.

Over the past decade, researchers in the Niederweis lab at UAB have advanced siderophore knowledge for M. tuberculosis, or Mtb. In 2013, they described two small membrane proteins that are required for siderophore secretion by Mtb, through their association with known efflux pumps to comprise a siderophore export system at the inner membrane.

In 2014, they described how a double mutant of those two small proteins left the Mtb exquisitely sensitive to tiny concentrations of the Mtb siderophore mycobactin, a toxicity phenomenon they named siderophore poisoning.

In 2020, they described how mutation of another Mtb gene, rv0455c, showed the same phenotype as deletion of the two small proteins siderophore poisoning in the presence of mycobactin. Furthermore, the rv0455c gene is located close to the gene location for the two small proteins that are essential for siderophore efflux. Therefore, the UAB researchers hypothesized that rv0455c also would function in siderophore secretion.

That was correct, as they report in the Nature Communications study, A periplasmic cinched protein is required for siderophore secretion and virulence of Mycobacterium tuberculosis.

Using a variety of genetic and biochemical approaches, they showed that the rv0455c gene is essential for Mtb to grow in low-iron medium, and that the secretion of the two Mtb siderophores mycobactin and carboxymycobactin is drastically reduced in the rv0455c deletion mutant.

Although quantities of the Rv0455c protein are found outside of growing Mtb cells, Zhang and Niederweis found that a genetically engineered Rv0455c variant designed to anchor in the Mtb inner membrane was functional in siderophore secretion, supporting an intracellular role for Rv0455c. Deletion of Rv0455c from a virulent strain of Mtb severely impaired replication of M. tuberculosis in mice, demonstrating the importance of Rv0455c and siderophore secretion during disease.

The rv0455c gene in Mtb has no sequence homology with genes in bacteria like E. coli, but it is one of the core genes found in Mycobacteria, with a high degree of homology among the various homologs. Prior to the current study, Rv0455c had been annotated as a protein of unknown function.

The researchers found that genes homologous to rv0455c from M. smegmatis, M. leprae and M. haemophilium were fully functional in Mtb, restoring its growth in the presence of mycobactin. The crystal structure of the homologous protein from M. smegmatis showed a disulfide bond in the protein, producing a cinched structure, and the protein presents two surface patches of amino acids that are evolutionarily conserved among the Mycobacteria.

The mechanistic function of Rv0455c is still unknown, and the protein does not show the deep cleft commonly found in siderophore-binding proteins. However, Rv0455c may play an important structural role in the siderophore secretion system of Mtb, researchers say, possibly by acting as an essential accessory protein or by connecting the inner-membrane siderophore exporters with a putative outer membrane channel.

This study presents a major step forward in understanding the Mtb siderophore secretion system, whose proteins have no similarities to other bacterial siderophore secretion systems, Niederweis said. Furthermore, we identify siderophore poisoning as an important mechanism of the large virulence loss of the Mtb mutant lacking the rv0455c gene, validating siderophore secretion as a drug target and revealing a new mechanism for putative tuberculosis drugs.

At UAB, Niederweis is a professor and Zhang is a researcher v in the Department of Microbiology in the Marnix E. Heersink School of Medicine.

Co-authors with Niederweis and Zhang are James E. Kent, Alexander E. Aleshin and Francesca M. Marassi, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Meredith Whitaker and Sabine Ehrt, Weill Cornell Medical College, New York, New York; David C. Young and D. Branch Moody, Harvard Medical School, Boston, Massachusetts; Dominik Herrmann and Jamil S. Saad, UAB Department of Microbiology; and Ying-Hui Ko and Gino Cingolani, Thomas Jefferson University, Philadelphia, Pennsylvania.

Support came from National Institutes of Health grants AI049313 and AI151239.

At UAB, Niederweis holds the Triton Endowed Professorship in Bacteriology.

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A gene in tuberculosis bacteria is found essential for siderophore secretion and virulence - University of Alabama at Birmingham

The following discussion should be read in conjunction with the unauditedConsolidated Financial Statements and the notes thereto included in thisQuarterly Report on Form 10-Q and the audited Consolidated Financial Statementsand the notes thereto included in our Annual Report on Form 10-K for the fiscalyear ended December 31, 2021. Some of the statements we make in this section areforward-looking statements within the meaning of the federal securities laws.Some of the statements we make in this section are forward-looking statementswithin the meaning of the federal securities laws. For a complete discussion offorward-looking statements, see the section in this Quarterly Report on Form10-Q entitled "Special Note Regarding Forward-Looking Statements". Certain riskfactors may cause actual results, performance or achievements to differmaterially from those expressed or implied by the following discussion. For adiscussion of such risk factors, see the section in our Annual Report on Form10-K for the fiscal year ended December 31, 2021 entitled "Risk Factors".

Overview

We are a global, patient-dedicated biotechnology company focused on discovering,developing, and delivering novel medicines for rare diseases. We have aportfolio of product opportunities including the first, oral monotherapy forFabry disease that has achieved widespread global approval and a differentiatedbiologic for Pompe disease that is under review with the U.S. Food and DrugAdministration ("FDA") as well as the European Medicines Agency ("EMA"). We arecommitted to discovering and developing next generation therapies in Fabry andPompe diseases.

The cornerstone of our portfolio is Galafold (also referred to as"migalastat"), the first and only approved oral precision medicine for peopleliving with Fabry disease who have amenable genetic variants. Migalastat iscurrently approved under the trade name Galafold in the United States ("U.S."),European Union ("E.U."), United Kingdom ("U.K."), and Japan, with multipleadditional approvals granted and applications pending in several geographiesaround the world.

The lead biologics program of our pipeline is Amicus Therapeutics GAA ("AT-GAA",also known as ATB200/AT2221, or cipaglucosidase alfa/miglustat), a novel,two-component, potential best-in-class treatment for Pompe disease. In February2019, the FDA granted Breakthrough Therapy designation ("BTD") to AT-GAA for thetreatment of late onset Pompe disease. In September 2021, the FDA set thePrescription Drug User Fee Act ("PDUFA") target action date of May 29, 2022 forthe New Drug Application ("NDA") for miglustat and July 29, 2022 for theBiologics License Application ("BLA") for cipaglucosidase alfa. The EMAvalidated the Marketing Authorization Application ("MAA") in the fourth quarterof 2021. On May 9, 2022, the FDA extended the review period for the NDA formiglustat and the BLA for cipaglucosidase alfa resulting in revised PDUFA actiondates of August 29, 2022 and October 29, 2022, respectively.

Our Strategy

Our strategy is to create, manufacture, test, and deliver the highest qualitymedicines for people living with rare diseases through internally developed,jointly developed, acquired, or in-licensed products and product candidates thathave the potential to obsolete current treatments, provide significant benefitsto patients, and be first- or best-in-class. We are leveraging our globalcapabilities to develop and broaden our lead franchises in Fabry and Pompedisease, with focused discovery work on next generation therapies and novelplatform technologies.

Our operations have not been significantly impacted by the novel coronavirus("COVID-19") pandemic thus far. The Company continued to observe increased lagtimes between patient identification and Galafold initiation due to theresurgence of COVID-19 in certain markets. We have maintained operations in allgeographies, secured our global supply chain for our commercial and clinicalproducts, as well as maintained the operational integrity of our clinicaltrials, with minimum disruptions. Our ability to continue to operate without anysignificant disruptions will depend on the continued health of our employees,the ongoing demand for Galafold and the continued operation of our globalsupply chain. We have continued to provide uninterrupted access to medicines forthose in need of treatment, while prioritizing the health and safety of ourglobal workforce. However, our results of operations in future periods may benegatively impacted by unknown future impacts from the COVID-19 pandemic.

Highlights of our progress include:

Commercial and regulatory success in Fabry disease. For the three months endedMarch 31, 2022, Galafold revenue totaled $78.7 million, an increase of $12.3million compared to the same period in the prior year. We continue to see strongcommercial momentum and expansion into additional geographies. In countrieswhere we have been operating the longest, we see an increasing proportion ofpreviously untreated patients come onto Galafold. In the U.S., we

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continue to see a significant increase in patients from a growing and very wideprescriber base. Across all markets, we see a high rate of compliance andadherence to this oral treatment option.

Pompe disease clinical program milestones. In February 2021, we reportedtopline results from the Phase 3 study of AT-GAA (ATB200-03, also known as"PROPEL"). In June 2021, the MHRA granted AT-GAA a positive scientific opinionthrough the Early Access to Medicines Scheme ("EAMS") which permits eligibleadults living with late-onset Pompe disease ("LOPD") who have receivedalglucosidase alfa for at least 2 years to switch to AT-GAA prior to marketingauthorization in the U.K. We completed the submission of the rolling BLA and NDAto the FDA, which was accepted for review in September 2021, and in the fourthquarter of 2021, the MAA was submitted and validated by the EMA. In March 2022,we announced positive long-term data from our ongoing phase 1/2 clinical study.Study participants treated with AT-GAA for up to 36 months demonstratedpersistent and durable effects on six-minute walk test distance and measures ofmotor function and muscle strength, stability, or increase in forced vitalcapacity, and reductions in biomarkers of muscle damage and disease substrate.

Pipeline advancement and growth. We are leveraging our global capabilities todevelop and broaden our lead franchises in Fabry and Pompe disease, with focuseddiscovery work on next generation therapies and novel platform technologies.

Manufacturing. We have managed our clinical and commercial supply chains duringthe COVID-19 pandemic such that as of the date hereof we have not experiencedsupply impacts. We have been able to continue to meet required commercial demandfor Galafold as well as supply our ongoing Pompe disease clinical studies andaccess programs including EAMS without interruption. We have secured supply forour continued needs for the Pompe disease program through a long-term supplyagreement with Wuxi Biologics. The agreement allows for the continuousmanufacture of our biologic to support future clinical needs and our anticipatedcommercial requirements should we garner regulatory approvals as planned. Wehave contracts in place to supply miglustat, our small molecule component ofAT-GAA, to support both clinical and future commercial requirements.

Financial strength. Total cash, cash equivalents, and marketable securities asof March 31, 2022 was $411.2 million. Based on the current operating model, webelieve that the current cash position, which includes expected revenues, issufficient to fund our operations and ongoing research programs to achieveself-sustainability. Potential impacts of the COVID-19 pandemic, businessdevelopment collaborations, pipeline expansion, and investment in manufacturingcapabilities could impact our future capital requirements.

Our Commercial Product and Product Candidates

Galafold (Migalastat HCl) for Fabry Disease

Our oral precision medicine Galafold was granted accelerated approval by theFDA in August 2018 under the brand name Galafold for the treatment of adultswith a confirmed diagnosis of Fabry disease and an amenable galactosidase alphagene ("GLA") variant based on in vitro assay data. The FDA has approvedGalafold for 350 amenable GLA variants. Galafold was approved in the E.U. andU.K. in May 2016 as a first-line therapy for long-term treatment of adults andadolescents, aged 16 years and older, with a confirmed diagnosis of Fabrydisease and who have an amenable mutation (variant). The approved E.U. and U.K.labels include 1,384 mutations amenable to Galafold treatment, which representup to half of all patients with Fabry disease. In countries where mutations areprovided only on the amenability website, these 1,384 amenable mutations are nowavailable. Marketing authorization approvals have been granted in over 40countries around the world, including the U.S., E.U., U.K., Japan, and others.In July 2021, Galafold was approved in the E.U. for adolescents aged 12 yearsand older weighing 45 kg or more. We plan to continue to launch Galafold inadditional countries during 2022, including for adolescents aged 12 years andolder.

As an orally administered monotherapy, Galafold is designed to bind to andstabilize an endogenous alpha-galactosidase A ("alpha-Gal A") enzyme in thosepatients with genetic variants identified as amenable in a GLP cell-basedamenability assay. Galafold is an oral precision medicine intended to treatFabry disease in patients who have amenable genetic variants, and at this time,it is not intended for concomitant use with ERT.

In early 2022, we announced the issuance of six additional patents, includingthe new U.S. Composition of Matter patent, for the Galafold intellectualproperty. Galafold now has 35 issued patents, 18 of which provide protectionthrough 2038.

Next Generation for Fabry Disease

We are committed to continued innovation for all people living with Fabrydisease. Our pipeline includes a Fabry gene therapy.

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Novel ERT for Pompe Disease

We are leveraging our biologics capabilities to develop AT-GAA, a noveltreatment paradigm for Pompe disease. AT-GAA consists of a uniquely engineeredrhGAA enzyme, ATB200, or cipaglucosidase alfa, with an optimized carbohydratestructure to enhance lysosomal uptake, administered in combination with AT2221,or miglustat, that functions as an enzyme stabilizer. Miglustat binds to andstabilizes ATB200, or cipaglucosidase alfa, preventing inactivation of rhGAA incirculation to improve the uptake of active enzyme in key disease-relevanttissues, resulting in increased clearance of accumulated substrate, glycogen.Miglustat is not an active ingredient that contributes directly to substratereduction ("glycogen").

In February 2021, we reported topline results from the Phase 3 PROPEL study. Ofthe Pompe disease patients enrolled, 77% were being treated with alglucosidasealfa (n=95) immediately prior to enrollment ("Switch") and 23% had never beentreated with any ERT (n=28) ("Nave"). Nearly all patients from the PROPEL studycontinue to be treated with AT-GAA in the extension clinical study. The clinicaldata from the PROPEL study, the extension study as well as the Phase 1/2 studywere included in the AT-GAA submissions to the FDA and the EMA.

In March 2022, we announced positive long-term data from our ongoing phase 1/2clinical study. Study participants treated with AT-GAA for up to 36 monthsdemonstrated persistent and durable effects on six-minute walk test distance andmeasures of motor function and muscle strength, stability, or increase in forcedvital capacity, and reductions in biomarkers of muscle damage and diseasesubstrate.

In addition, we are conducting ongoing clinical studies in pediatric patientsfor both LOPD and infantile-onset Pompe disease ("IOPD") populations.

Next Generation for Pompe Disease

As part of our long-term commitment to provide multiple solutions to address thesignificant unmet needs of the Pompe disease community, we are also continuingdiscovery for next-generation genetic medicines for Pompe disease.

CDKL5 Deficiency Disorder

We are researching a potential first-in-class genetic medicine for CDKL5deficiency disorder consisting of a CDKL5 protein engineered for crosscorrection, delivered as either a protein replacement or as a gene therapythrough our collaboration with Penn. We are collaborating with the LouLouFoundation to assess the natural history of the disease to identify endpointsfor potential use in future studies.

Additional Next Generation Programs

We have a number of additional gene therapies in clinical and preclinicaldevelopment, including potential gene therapies in multiple forms of Battendisease.

Strategic Alliances and Arrangements

We will continue to evaluate business development opportunities as appropriateto build stockholder value and provide us with access to the financial,technical, clinical, and commercial resources necessary to develop and markettechnologies or products with a focus on rare and orphan diseases. We areexploring potential collaborations, alliances, and other business developmentopportunities on a regular basis. These opportunities may include businesscombinations, partnerships, the strategic out-licensing of certain assets, orthe acquisition of preclinical-stage, clinical-stage, or marketed products orplatform technologies consistent with our strategic plan to develop and providetherapies to patients living with rare and orphan diseases.

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Edgar Online, source Glimpses

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AMICUS THERAPEUTICS, INC. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-Q) - Marketscreener.com

For countries that could get their hands on it, the rapid development of mRNA vaccines for COVID-19 was something close to a miracle, saving an estimated 1.1 million lives in the United States alone.

By capitalizing on recent developments in gene sequencing, chemical synthesis and new delivery mechanisms, scientists were able to start the first clinical trials for mRNA vaccines just four months after the World Health Organization declared a pandemic. This success, industry observers say, could act as a kind of blueprint to tackle other hard-to-treat diseases.

It was really the development of several technologies coming together that put us in a position where we were able to respond very, very quickly, says Richard Bozzato, a senior adviser on health at MaRS. It showed we can do it.

Researchers are using these advances to speed up all aspects of drug development from discovery to how a medication is administered with the potential to cut costs, save time and help more patients. The whole objective here, says Bozzato, is to be able to cure as many patients as we can.

Using AI to speed up drug development

Fewer than 10 per cent of new compounds ever make it from the test tube to clinical use. Most turn out to be either less effective or more toxic than originally believed. Even then, many drugs that are approved can have serious side effects.

Right now, the process of discovery and development is hit and miss, says Bozzato. You do an experiment and see what happens. Then you discover something you didnt expect. This is where artificial intelligence and machine learning can help: by running tests through computational models, they can identify issues as well as promising new compounds much faster.

If you can combine the speed of computational approaches with the intuition and brilliance of the human mind, you can start asking different questions for a different problem, says Naheed Kurji, co-founder, president and CEO of Toronto-based Cyclica. It means more medicines, better medicines faster. We wont have to wait 12 years to get them.

Researchers have been developing computational techniques to pinpoint the molecular drivers of disease for more than 20 years, but the area has expanded considerably in the last five years as more genetic data becomes available. A major breakthrough came last year when Googles artificial intelligence startup Deep Mind allowed free access to its AlphaFold database of three-dimensional protein structures.

The program predicts those structures with more than 90 per cent accuracy twice the accuracy of previous programs. Work that would have taken months or years can now be accomplished in a few hours or days, says Bozzato.

More than 400 companies worldwide are now working in the space, targeting diseases from Alzheimers and Parkinsons disease to various forms of cancer. Cyclica is looking into new treatments for a range of ailments that are hard to treat, including some central nervous system disorders such as pain and spinal disease. And Deep Genomics, another Toronto-based venture, is preparing its first AI-discovered drug programs for clinical trials.

Finding a better delivery mechanism

Medications are only effective if they end up in the right place, at the right time. When theyre on target, they can treat disease in the affected tissues with minimal side effects. Researchers have been developing safe and effective drug delivery technologies for decades, but new, more complex therapies such as mRNA and gene editing need more complex delivery systems. Thats where lipid nanoparticles come in.

Lipid nanoparticles are the tiny envelopes that deliver the active ingredient in mRNA COVID vaccines. Their success in the mRNA vaccines suggests they have much greater potential to safely deliver other innovative therapies, such as small drugs, proteins or genetic material.

Seeing the safety and efficacy of these vaccines was proof you could use this for a new modality, says Brent Stead, co-founder and chief executive officer of Specific Biologics, a discovery-stage gene-editing company thats experimenting with lipid nanoparticles to deliver gene therapy. If it works in this application, then fundamentally theres no reason it cannot work in others.

The particles, which are fatty molecules that closely resemble human cells, act as a protective layer for small molecule therapies as they make their way to their target cells. Their close resemblance to human cells means they can evade the bodys natural defences, making them non-toxic. Theyre especially effective at reaching specific organs or cells because they can have chemical structures attached to their surface that recognize unique molecules on their targets.

Researchers are looking to see whether lipid nanoparticles can be used to deliver the CRISPR gene-editing technology to target rare diseases that are caused by a single genetic mutation, such as ALS, Huntingtons Disease and ocular diseases that cause blindness. You can envision a treatment where you do the treatment once and that permanently corrects the disease, says Stead.

California-based Intellia Therapeutics recently started the first clinical safety trials using the combination to target liver diseases, and Specific Biologics is doing laboratory research on illnesses that affect the lungs, such as cystic fibrosis.

Treatments are still several years away, however. Although CRISPR works in animal models, researchers are still determining how to get it to consistently target a specific genetic mutation without damaging other cells. Another challenge, Stead says, is the fact that lipid nanoparticles tend to accumulate in the liver, making them most effective for targeting liver disease. Biotech companies are now working on next-generation LNPs that target different tissues and organs.

Creating a tailored treatment

One of the challenges in treating cancer is that cancer cells are constantly looking for ways to survive. They may respond initially to a treatment but then mutate and develop a resistance. Doctors then need to find a new treatment. In other cases, patients dont respond to therapy at all. Scientists are turning to next-generation sequencing to find the treatment that can be tailored to the individual patient, as well as determine why a treatment has failed.

Xue Wu, a co-founder of Geneseeq, one of the companies specializing in this field, recalls one woman who wasnt responding to traditional chemotherapy for an advanced sarcoma and was on life support in the ICU. Using next-generation sequencing, Wu discovered that a rare genetic mutation might have caused the resistance. She helped her join a clinical trial for a new drug targeting that mutation. Within 10 days, the tumour had dramatically reduced in size, and the woman lived for another 10 months before she developed drug resistance to this drug and died.

Next-generation sequencing can map hundreds of genes at a time and find the mutation in as little as five days, so that doctors can find treatments that target only those cells. Since the U.S.-based Foundation Medicine made the technique commercially available a decade ago, its application in the U.S. and other countries has grown rapidly. The technique has been especially useful in lung cancer, Wu says, for which several generations of precision treatments are available. You have the option to choose different drugs, so the patient will have a prolonged lifespan. It significantly improves the five-year survival rate of these patients.

The next frontier, Wu adds, is developing more precise treatments for other types of cancer mutations currently without viable treatment options. Researchers are now looking at whether technologies such as CRISPER gene editing and mRNA vaccines, could be deployed.

Scaling up treatments

The other big challenge for Canadian companies working to speed up drug development lies outside the laboratory, in the commercial realm, says Bozzato. The success of COVID vaccines proved that many Canadian researchers are leaders in drug development. For example, Peter Culis, now a professor emeritus at the University of British Columbia, was one of the pioneers in developing lipid nanoparticles. The B.C. company Genevent Sciences Corporation supplies LNPs to mRNA vaccine manufacturers Pfizer-BioNTech and Moderna.

However, as a recent report from the Innovation Economy Council notes, Canada doesnt currently have the large-scale manufacturing facilities that could help translate homegrown research into homegrown therapies. The federal government has started to address the issue, investing $1.2 billion in various projects, which could help Canada secure a slice of the growing global biotech industry.

The MaRS Impact Health conference, being held May 25 to 27, explores the latest innovations in biotech.

Anita Elash is a freelancer who write about technology for MaRS. Torstar, the parent company of the Toronto Star, has partnered with MaRS to highlight innovation in Canadian companies.

Disclaimer This content was produced as part of a partnership and therefore it may not meet the standards of impartial or independent journalism.

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The success of mRNA vaccines could act as a blueprint to tackle other diseases - Toronto Star

Did you know that viruses can kill bacteria? It's true and the process holds much promise for medicine.

For the first time ever, researchers successfully used bacteriophages to treat an antibiotic-resistant mycobacterial lung infection. This process led the way for a young National Jewish Health patient with cystic fibrosis to receive a life-saving lung transplant, according to a press release by the institution published on Friday.

We had tried unsuccessfully for years to clear the mycobacterial infection with a variety of antibiotics, said Jerry Nick, MD, lead author of the study and director of the Adult Cystic Fibrosis Program at National Jewish Health. When we used the bacterias own natural enemies, we were able to clear the infection which resulted in a successful lung transplant.

No one was happier with the results of the treatment than the patient himself.

I am so grateful for the effort, persistence, and creativity of all the people who were involved in my treatment, said Jarrod Johnson, recipient of the lung transplant. I thought I was going to die. They have literally saved my life.

Johnson is a 26-year-old cystic fibrosis patient who has been plagued with repeated lung infections starting from childhood and causing him to be admitted to various hospitals several times a year.

In adulthood, he suffered from a rapid decline in his lung function due to a persistentMycobacterium abscessusinfection over a six-year period that caused doctors to believe he was likely to die in only a few years without a lung transplant. However, hehad been refused transplants by three transplant centers because of his continuous mycobacterial infection.

That's when Nick and his team decided to treat him with phages (viruses that attack bacteria) for the first time ever. The treatment ran for 200 days but proved so successful that Johnson was ready to undergo a lung transplant.

This research can serve as a roadmap for future use of phages to treat patients with severeMycobacterium abscessuslung infection and to save lives, concluded Nick.

Abstract:Two mycobacteriophages were administered intravenously to a male with treatment-refractoryMycobacterium abscessuspulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyseM.abscessusand were selected specifically as the most effective against the subjects bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments.M.abscessusisolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detectM.abscessus. This study describes the course and associated markers of a successful phage treatment ofM.abscessusin advanced lung disease.

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Researchers have used a virus to fight a drug-resistant lung infection - Interesting Engineering