Category Archives: Gene Medicine

DUBLIN--(BUSINESS WIRE)--The "Global Regenerative Medicine Market Size, Share & Trends Analysis Report by Product (Cell-based Immunotherapies, Gene Therapies), by Therapeutic Category (Cardiovascular, Oncology), and Segment Forecasts, 2021-2027" report has been added to ResearchAndMarkets.com's offering.

The global regenerative medicine market size is expected to reach USD 57.08 billion by 2027, growing at a CAGR of 11.27% over the forecast period.

Recent advancements in biological therapies have resulted in a gradual shift in preference toward personalized medicinal strategies over the conventional treatment approach. This has resulted in rising R&D activities in the regenerative medicine arena for the development of novel regenerative therapies.

Furthermore, advancements in cell biology, genomics research, and gene-editing technology are anticipated to fuel the growth of the industry. Stem cell-based regenerative therapies are in clinical trials, which may help restore damaged specialized cells in many serious and fatal diseases, such as cancer, Alzheimer's, neurodegenerative diseases, and spinal cord injuries.

For instance, various research institutes have adopted Human Embryonic Stem Cells (hESCs) to develop a treatment for Age-related Macular Degeneration (AMD).

Constant advancements in molecular medicines have led to the development of gene-based therapy, which utilizes targeted delivery of DNA as a medicine to fight against various disorders.

Gene therapy developments are high in oncology due to the rising prevalence and genetically driven pathophysiology of cancer. The steady commercial success of gene therapies is expected to accelerate the growth of the global market over the forecast period.

Regenerative Medicine Market Report Highlights

Key Topics Covered:

Market Variables, Trends, & Scope

Competitive Analysis

Covid-19 Impact Analysis

Regenerative Medicine Market: Product Business Analysis

Regenerative Medicine Market: Therapeutic Category Business Analysis

Regenerative Medicine Market: Regional Business Analysis

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/kovhgl

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Global Regenerative Medicine Market is Expected to Reach USD 57.08 Billion by 2027, Growing at a CAGR of 11.27% Over the Forecast Period. -...

Researchers at the Australian National University (ANU) report in Cell Reports Medicine that they have identified a mutation in the gene VANGL1 that causes the development of kidney disease. It joins other genetic variations known to increase kidney disease risk such as certain variants in the MYH9 and APOL1 genes. Further testing of the VANGL1 mutations also revealed that the gene helps prevent the immune system from attacking the kidney.

The findings are published in the journalCell Reports Medicinein a paper titled, Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease.

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high-risk populations through a kidney-intrinsic process, the researchers wrote. Half of all systemic lupus erythematosus (SLE) patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE. We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients.

The researcherssequenced the genome of patients with autoimmune kidney disease and Tiwi Islanders with extremely high rates of kidney disease.

Patients with this mutation will be significantly more likely to develop kidney disease, lead author, nephrologist, and ANU research fellow, Simon Jiang, Ph.D., said.

This discovery has big implications for Tiwi Islanders. They have the highest recorded rates of kidney disease in the world.

When you have a systemic immune or inflammatory disease, this mutation allows the immune system to attack the kidney. The natural function of this gene is to slow that inflammatory process down, Jiang explained.

People think immune diseases such as lupus happen to attack the kidneys by chance. What we have actually shown for the first time is that the kidney has its own way of resisting or stopping that assault.

The new findings highlight the evolving role of VANGL1 and other PCP genes in kidney injury and repair, which may have important implications for therapeutics and transplantation.

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Gene Mutation Found that is Linked to the Development of Kidney Disease - Clinical OMICs News

Seven people who underwent heart-bypass surgery recently in Europe volunteered to receive an additional treatment: injections of messenger RNA.

This was not one of the COVID-19 vaccines, in which the RNA code is used to teach the recipients immune system. Instead, the RNA for the surgery patients was designed to heal their hearts by promoting the growth of new blood vessels.

The study, a collaboration between drugmakers AstraZeneca and Moderna, is among dozens underway to harness the potential of RNA. Some of them started before the pandemic, but with the real-world success of the vaccines, they have now picked up steam.

At Duke University Medical Center, researchers are testing a different RNA-based drug from Moderna in patients with propionic acidemia, a rare disorder in which the liver is unable to break down certain amino acids and fats. Others are testing messenger RNA against a variety of cancers.

And, of course, RNA is being used to make more vaccines. Among those being tested are vaccines against Zika virus, respiratory syncytial virus (RSV), cytomegalovirus, and the flu.

All these efforts rely on RNAs ability to carry the recipe for proteins, the building blocks of life. In a vaccine, the protein is a harmless fragment of the virus in question, allowing the recipients immune system to practice in the event of infection. In the other drugs, the RNA can prompt patients cells to make beneficial proteins that they are unable to make themselves.

It is too soon to say how well the various non-vaccine RNA drugs will work, said cardiologist Howard J. Eisen, a medical director at the Penn State Heart and Vascular Institute, who has been following the research. Among other issues: RNA degrades quickly (remember how the COVID vaccines require cold storage?), so it has to be delivered to the right cells in a timely fashion.

Yet the potential, he says, is vast.

Itll revolutionize medicine, I think.

In the heart study, patients experienced no serious side effects as a result of the injections, the drugmakers reported in November. That was little surprise, given that billions have now been injected safely with RNA vaccines, said Eisen, who was not involved with the study.

But with just seven people (and another four who received placebo injections), the study was too small to draw conclusions about the drugs effect on heart function. Larger studies are planned.

The RNA carries the recipe for a protein called VEGF-A, a growth factor involved in forming new blood vessels. The hope is that the patients would experience an improved ejection fraction a measure of how much oxygenated blood is pumped with each heartbeat. Yet previous studies, in which researchers have sought to boost that protein with a different approach called gene therapy, have met with limited success.

Likewise, tests of the RNA-based drug for propionic acidemia are in the early stages, as are studies of RNA treatments for other metabolic diseases.

Whats clear is that new approaches for these liver disorders are sorely needed, said Dwight Koeberl, who is overseeing the Duke University site for Modernas propionic acidemia trial.

For now, patients with that disease must severely limit or avoid intake of meat, dairy, and nuts or else their bodies build up toxic byproducts that lead to neurological and heart damage, among other complications. To compensate for this restricted diet, they must drink a special formula with vitamins and other supplements. And even so, some eventually need a liver transplant.

Koeberl, a professor of pediatrics at Duke University School of Medicine, also has studied the use of gene therapy to treat such patients. That approach is a long-term fix, as the instructions for making the corrective proteins are delivered inside the nucleus of the persons cells (whereas RNA is transient, degrading within days meaning that some treatments would need to be administered multiple times).

But as with the gene therapy treatments for heart disease, gene therapy for metabolic disorders remains a work in progress. One hurdle with gene therapy is that it is typically delivered inside the recipients cells with a virus, which can be defeated by the immune system, Koeberl said.

RNA-based therapies, on the other hand, are typically packaged in tiny droplets of oily molecules called lipids, as with the COVID vaccines. These lipid nanoparticles do not enter the cell nucleus. They need to penetrate only the outer cell membrane for the RNA to fulfill its mission, and they do so with ease. Koeberl was attracted by the possibility of a more straightforward solution.

My interest is in trying to help these patients with something sooner rather than later, he said.

Many, if not most, of the RNA drugs being tested are vaccines, to judge from a search of clinicaltrials.gov, a listing of clinical studies maintained by the U.S. National Library of Medicine.

Compared to traditional vaccines, one advantage of the RNA approach is that the genetic instructions can be quickly updated to match emerging threats. Pfizer and BioNTech, for example, already are developing a vaccine to match the omicron variant of the coronavirus, though widescale production still takes time. The European Union has ordered 180 million doses of this modified vaccine, expected to be available by March.

Next-generation RNA vaccines may also have the advantage of requiring lower doses. Thats the idea behind a flu vaccine in development by Seqirus, which has U.S. operations in Summit, N.J., and is a subsidiary of CSL Limited, based in Melbourne, Australia.

The RNA in that vaccine is self-amplifying, meaning that it consists of two elements: the genetic recipe for making flu proteins that stimulate an immune response, as well as instructions to make multiple copies of that recipe. In theory, that would mean a lower dose of such a vaccine could be just as effective, yet with a lower rate of side effects. Seqirus has been studying this approach in animal models for years, and it plans to test this type of flu vaccine in human volunteers during the second half of 2022.

Patient support groups have been watching the development of messenger RNA with great interest, whether the drug is being used to prevent disease, as with the vaccines, or to treat it.

Many advocates were aware of the potential for RNA treatments long before the COVID vaccines came out. Among them is Kathy Stagni, executive director of the Organic Acidemia Association, which provides support for patients with propionic acidemia and others.

She said she has been setting the record straight every time she hears someone claim that the technology behind the COVID vaccines was rushed.

This is something theyve been working on for a long time, she said.

Eisen, the Penn State cardiologist, was working at the University of Pennsylvania decades ago when Penn scientist Katalin Karik was doing some of the early experiments that would set the stage for the vaccines.

She was not working on vaccines at the time, but on using messenger RNA to treat heart disease. Now that the technology has matured, AstraZeneca and Moderna are tackling heart disease once again.

In essence, Eisen said, it has come full circle.

Read more:
Vaccines are just the beginning for RNA. The technology is being tested on heart and liver diseases. - The Philadelphia Inquirer

Today, you could estimate that one family per day is being treated with and impacted by gene therapy. We want to see that increase to 10s, 100s, 1,000s per day, and reaching that goal comes from investing in research, clinical trials and manufacturing, said Ken Mills, CEO of clinical stage US biotechnology company, Regenxbio.

Regenxbio, said its CEO, has played a pivotal role in the gene therapy industry since its founding in 2008, as a result of research from the lab of gene therapy pioneer, Jim Wilson, University of Pennsylvania.

The company's NAV technology platform consists of over 100 novel adeno-associated virus (AAV) vectors, one of which was used in the US Food and Drug Administration (FDA) approved gene therapy, ZOLGENSMA, for spinal muscular atrophy in children under two years old.

The developer has also licensed out its technology to a growing list of partners and licensees that includes Novartis, Eli Lily and Pfizer and has a robust in-house pipeline of candidates for retinal and rare diseases.

Looking at the US gene therapy regulatory landscape, what are the current roadblocks?

AAV-mediated gene therapies offer the possibility of a one-time administration that could address the underlying disease and change the way critical medicine is delivered to patients, but the regulatory landscape has not evolved as quickly as the innovations of AAV gene therapy.

Weve seen that the FDA is open to working with industry and gene therapy stakeholders to determine the appropriate path forward, to streamline clinical development and get medicines to patients faster. Leveraging accelerated approvals and surrogate endpoints in clinical trials, such as a biomarker, may play a large role, Mills told BioPharma-Reporter.

The Pathway Development Consortium (PDC) launched in 2021 by Regenxbio and Solid Biosciences is working to advance opportunities to leverage the FDAs accelerated approval pathway for gene therapy candidates.

Our mission to bring together patients, industry, regulators, academia, payers and other stakeholders for meaningful scientific and policy discussion, said the CEO.

There is a significant strain on manufacturing capabilities in the gene therapy sector both capacity and reproducibility, but more importantly, talent, commented Mills.

As the sector has grown rapidly and expanded broadly, we have seen these rate-limiting factors continue to persist. In addition, significant strain on supply chains is likely to continue into 2022 and will impact pharma and biotech. Consistent, reliable manufacturing is critical to gene therapy trial development, product approval, and commercialization, so it is crucial to overcome these capabilities challenges.

Contract development and manufacturing organizations (CDMOs) are critical partners, said the executive, and he anticipates continued investment in manufacturing capabilities through in-house facilities and CDMOs next year.

And as the field continues to advance, we will start to see more and more efficiencies that companies like Regenxbio can capitalize upon to allow for rapid manufacturing and formulation development.

Regenxbio has invested in the establishment of a robust suspension cell culture-based manufacturing process and new manufacturing facility at its headquarters in Rockville, Maryland.

We have also invested to ensure the hiring of the right people to make this possible. Five to 10 years ago, you did not see a lot of process development teams, and now they are crucial to drive the scalability of capabilities across clinical and commercial strategy.

Through the expansion of its expert manufacturing team and facility build out, he said the companys researchers and process development team have been able to work side by side to mitigate potential issues early in the development process.

The goal is always to get therapies approved and to patients as quickly as possible, and a reliable, scalable chemistry, manufacturing and controls (CMC) process is crucial in accomplishing this, said Mills.

Our philosophy initially was to develop the best process platform that could be utilized across multiple programs with a highly similar process that could be easily transferred to a CDMO. We also have a platform downstream process developed that works across our programs, giving consistent downstream yields that are appropriate for the current phase of development.

We have developed proprietary formulations that are indication-specific. The formulations are stable at the intended storage conditions over several years and we have ongoing monitoring of product quality during that period to ensure consistent performance.

In terms of the highlights for the biotech this year, Mills said it was a fast paced, high-achieving 12 months for the company.

In September, we announced a partnership with AbbVie to develop and commercialize RGX-314, our gene therapy for the treatment of wet AMD, diabetic retinopathy, and other chronic retinal diseases. Under the terms of the agreement, AbbVie will provide Regenxbio a US$370m upfront payment with the potential for the company to receive up to US$1.38bn in additional development, regulatory and commercial milestones.

We are currently running a pivotal program of RGX-314 for the treatment of wet AMD, and we expect to file a BLA in 2024. We are also conducting additional trials evaluating RGX-314 delivered directly to the suprachoroidal space of the eye for the treatment of wet AMD and diabetic retinopathy. In 2021, we reported initial data from both of those trials.

Regenxbio also announced, early in 2021, a new pipeline candidate for treating Duchenne muscular dystrophy (Duchenne) - RGX-202. That is designed, said Mills, to deliver an optimized microdystrophin transgene with a unique C-terminal domain and a muscle specific promoter to support targeted therapy for improved resistance to muscle damage associated with Duchenne.

We received Orphan Drug Designation from the FDA in November and shared that we expect to submit an Investigational New Drug (IND) application to the FDA for RGX-202 by the end of 2021.

Commercial-scale cGMP material has already been produced at 1,000 liter capacity using our suspension cell culture manufacturing process, and the company's internal cGMP facility is expected to allow for production up to 2,000 liters for the clinical development of RGX-202.

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A look at prospects for the US gene therapy industry - BioPharma-Reporter.com

Basel, December 22, 2021 Novartis announced today that it entered into a definitive agreement to acquire all of the outstanding share capital of the UK-based ocular gene therapy company Gyroscope Therapeutics.

Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss1. There are no approved treatments for GA, making it one of the most significant unmet needs remaining in retinal diseases2.

GT005 is designed as an AAV2-based, one-time investigational gene therapy for GA secondary to AMD that is delivered under the retina. GT005 aims to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein. Complement overactivation can lead to inflammation that damages healthy tissues, and it has been strongly correlated with the development and progression of AMD3. The CFI protein regulates the activity of the complement system. It is believed that increasing CFI production could reduce inflammation, with the goal of preserving a persons eyesight.

The safety and efficacy of GT005 for the treatment of GA secondary to AMD is currently being evaluated in a Phase 1/2 clinical trial and two Phase 2 clinical trials4,5,6. GT005 has received Fast Track designation from the U.S. Food and Drug Administration for the treatment of people with GA.

Gyroscope also has several additional assets in its pipeline in early discovery for retinal diseases.

With our own pioneering research in ocular gene therapies and our experience gained from bringing Luxturna to inherited retinal dystrophy patients outside of the US, Novartis has a well-established expertise in ocular gene therapies that will position us well to continue developing this promising one-time treatment said Marie-France Tschudin, President, Novartis Pharmaceuticals. This acquisition is one more step forward in our commitment to delivering innovation in ophthalmology to treat and prevent blindness worldwide.

Novartis will make an upfront payment of $800 million and potential additional milestone payments of up to $700 million. Closing of the transaction is subject to customary closing conditions including regulatory approvals. Until closing, Novartis and Gyroscope Therapeutics will continue to operate as separate and independent companies.

About geographic atrophy (GA)Dry AMD is a leading cause of permanent vision loss in people over the age of 55 and is a devastating diagnosis2,7.As dry AMD advances, it leads to GA, an irreversible degeneration of retinal cells, causing a gradual and permanent loss of central vision. This disease can severely impact a persons daily life as they lose the ability to drive, read and even see faces7.DisclaimerThis press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as potential, will, plan, could, commitment, investigational, to acquire, to develop, or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for GT005, the acquisition of Gyroscope Therapeutics, or regarding potential future revenues from GT005. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that GT005 will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee expected benefits or synergies from this transaction will be achieved in the expected timeframe, or at all, nor can there be any guarantee that GT005 will be commercially successful in the future. In particular, our expectations regarding GT005 or the transaction described in this media update could be affected by, among other things, the satisfaction of customary closing conditions including regulatory approvals, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AGs current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise.

About NovartisNovartis is reimagining medicine to improve and extend peoples lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the worlds top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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References1 Schmitz-Valckenberg S, et al. Natural History of Geographic Atrophy Progression Secondary to Age-Related Macular Degeneration (Geographic Atrophy Progression Study) Ophthalmology 2016;123:361-368.2 National Institute of Health. Age-Related Macular Degeneration. Accessed December 2021. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration. 3 Holz FG, et al. Geographic Atrophy: Clinical Features and Potential Therapeutic Approaches. Ophthalmology 2014;121(5):1079-1091. 4 U.S. National Library of Medicine. EXPLORE: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005 (EXPLORE). Accessed December 2021.https://clinicaltrials.gov/ct2/show/NCT04437368?term=geographic+atrophy%2C+GT005&cond=Macular+Degeneration&draw=2&rank=1#contacts5 U.S. National Library of Medicine. HORIZON: A Phase II Study to Evaluate the Safety and Efficacy of Two Doses of GT005. Accessed December 2021.https://clinicaltrials.gov/ct2/show/NCT04566445?term=GT005&draw=26 U.S. National Library of Medicine. FocuS: First in Human Study to Evaluate the Safety and Efficacy of GT005 Administered in Subjects With Dry AMD. Accessed December 2021.https://clinicaltrials.gov/ct2/show/NCT03846193?term=FOCUS&cond=Geographic+Atrophy&draw=2&rank=17 American Macular Degeneration Foundation. Macular Degeneration. Accessed December 2021. https://www.macular.org/what-macular-degeneration.

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Novartis to acquire Gyroscope Therapeutics, adding a one-time gene therapy that could transform care for geographic atrophy, a leading cause of...

STOCKHOLM, Dec. 23, 2021 /PRNewswire/ -- Betagenon AB a Sweden-based company focused on development of AMPK activator compounds, today announced the publication by co-founder Helena Edlund of a new study demonstrating the prevention and reversal of gene expression and epigenetic changes to beta cells in diet-induced obese mice. Treatment with O304 prevented genome-wide gene expression changes associated with high fat diet and remodelled active and repressive chromatin markers in beta cells, the cells responsible for producing the body's insulin. Glucose control was restored in the animals and markers of stress were reduced and markers of function increased in the beta cells.

The data are published in Scientific Reports, a member of the Nature family of journals.

"Obesity and associated insulin resistance stresses our beta-cells. If this persists long enough it will lead to beta-cell failure and the body will not be able to produce and secrete insulin, resulting in the development of diabetes. Our work identifies changes at the genetic level as the beta cells become stressed and show that these changes can be prevented by treatment with O304" said Prof. Helena Edlund of the Ume Centre for Molecular Medicine, and one of the senior authors of the study.

"A narrow window exists after diabetes onset when stressed beta cells can be rescued and their function normalized. These important results give us insight into the genetic changes involved in this process and are a key part in understanding the treatment potential of O304 in helping diabetic patients to remission" said Dr. James Hall, Betagenon CEO.

O304 is a first in class non-allosteric pan-AMPK activator. O304 sodium salt is in clinical development to treat Heart Failure, Renal Disease and Insulin Resistance.

Betagenon isa clinical stage company that develops its proprietary AMPK activators as therapies for diseases and conditions associated with the global epidemic in metabolic disorders and an aging population.

For more information, contact:

James Hall, CEO Betagenon AB

james.hall@betagenon.com+46 70 5775300

Helena Edlund received funding from Vetenskapsrdet, Familjen Erling-Perssons stiftelse, and

Knut och Alice Wallenbergs Stiftelse for the study.

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/betagenon-ab/r/betagenon-co-founder-publishes-that-ampk-activator-o304-prevents-gene-expression-changes-and-remobil,c3478094

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Betagenon co-founder publishes that AMPK activator O304 prevents gene expression changes and remobilisation of histone marks in islets of diet-induced...

In case you missed them the first time, take a look back through some of 2021s patient care and public health stories from the CUIMC Newsroom and other medical center sites:

The use of statins to reduce cholesterol is recommended for only a small fraction of young adults who have extremely high levels of LDL cholesterol. A study by VP&S researchers suggests that statins would provide lifetime health benefits for adults under 40 with less severely elevated levels of LDL cholesterol, preventing or delaying many heart attacks and strokes. It would also be cost-effective, particularly for young adult men. Read more.

VP&S researchers found that a single dose of ketamine not only reduced the severity of depression in people with suicide ideation, many of whom had not responded to other antidepressants, but also made them feel safer and less likely to harm themselves. Ketamine also improved neurocognitive skills such as thinking and reasoning.Read more.

The College of Dental Medicine unveiled its new mobile dental center, which will travel to Head Start centers, schools, senior centers, and other partner sites in CDMs Community DentCare Network. The clinic will deliver health screenings and low-cost dental care primarily to patients in Harlem, Washington Heights, Inwood, and the South Bronx. Read more.

Social media platforms are important sources of socialization and relationship-building for many young people, but they also can facilitate bullying and exclusion, promote unrealistic expectations about body image, and encourage risk-taking behaviors. In a Q&A, experts from VP&S and the Mailman School of Public Health shared their insights into social medias effect on the mental health of young people and adults and suggest everyone should consider periodic social media vacations. Read more.

TheU.S. Preventive Services Task Force, American Cancer Society, and American Society of Colorectal Surgery now recommend that people at average risk ofcolorectal cancerstart regular screenings at age 45 rather than 50. A VP&S surgeon explains why the change was made and what you need to know. Read more.

In September, Columbia Nursings faculty practice, thePrimary CareNurse Practitioner Group, celebrated five yearsofserving theWashington Heightscommunity. In that time, the group has recorded nearly 42,000 patient visits and 1,500 house calls.The groups services include on-site mental health services and a full range of primary care services for sexual and gender minority individuals. Because thegrouphad pilotedtelehealthinApril 2019,all ofthe practices NPs were experienced in providing remote care whenCOVID hit.In 2020, the group also served as a cough and fever clinic for COVID-19 patients. Read more.

The Cohen Center for Health and Recovery from Tick-Borne Diseases is the first in New York City to offer dedicated treatment for people with Lyme and related diseases. The center also has a national clinical trials network that will focus on identifying more effective treatments for patients with Lyme and tick-borne diseases. Read more.

A study of an investigational gene therapy for sickle cell disease has found that a single dose restored blood cells to their normal shape and eliminated the most serious complication of the disease for at least three years in some patients. Four patients at Columbia University Irving Medical Center/NewYork-Presbyterian participated in the multicenter study, the first to report such long-term outcomes of a sickle cell gene therapy. Read more.

New results from a long-term epidemiologic study reveal that one of the oldest racially based diagnostic formulas in medicine is no better than a race-neutral equation, suggesting the formula used to diagnose lung disease should be changed.Because the formula includes racial adjustments in defining normal lung function, Black people may be less likely to be treated with medications for COPD or diagnosed with other serious lung disorders compared to white people. Read more.

People who are trying to lose weight have a new option: A medication called semaglutide received FDA approval earlier this summer. In this Q&A, a VP&S weight loss expert explains how the drug works and who may benefit from it. Read more.

A new program at ColumbiaDoctors embeds behavioral health specialists alongside primary care providers to care for patients mental health needs. The program launched in November at all ColumbiaDoctors Primary Care locations to care for patients with depression. Expansion into other behavioral health needs, such as anxiety, substance use disorders, and attention deficit hyperactivity disorder, is planned for the future. Read more.

Columbia University Irving Medical Center with NewYork-Presbyterian has been named a Center of Excellence by the National Organization for Rare Disorders and joins a national network dedicated to improving treatment and care for people with rare diseases. Columbia was chosen as a Center of Excellence because it has experts across multiple specialties to meet the needs of patients with rare diseases and has a wide range of clinical, patient education, and research programs for people living with rare diseases. Read more.

The latest advance in radiation therapyusing artificial intelligence to adjust treatments as needed without delayis now available for select cancer patients at Columbia University Irving Medical Center/NewYork-Presbyterian. The new advance solves a long-standing issue in radiation oncology: the difficulty of adapting treatment to anatomical changes in the patient or the tumor that can occur during the many weeks of therapy. Read more.

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CUIMC Year in Review: Health News - Columbia University Irving Medical Center

In September 2021, following the publication of results from the phase 3 VISION trial of lutetium (Lu)-177 PSMA-617 (LuPSMA) in select patients with metastatic castration-resistant prostate cancer (mCRPC),1 the United States Food and Drug Administration (FDA) granted priority review to LuPSMA.2

The FDAs decision comes on the heels of the trials positive results, which are explored in How the VISION trial may change prostate cancer therapy, the fourth article in this Targeted Oncology series, entitled New Precision Medicine Approaches in Advanced Prostate Cancer. However, it also comes after recent advances in genetic testing, biomarkers, nuclear imaging, and combination treatments for prostate cancer. These are discussed, respectively, in The role of imaging and genomic testing in prostate cancer therapy, New horizons in nuclear medicine for prostate cancer, and Expert perspective on the changing treatment spectrum for advanced prostate cancer, also in this series.

As the FDA reviews LuPSMA, experts have questions about this novel radiopharmaceutical and how it might be adopted in the US.

Ahead, Oliver Sartor, MD, medical director at Tulane Cancer Center in New Orleans, Louisiana, co-principal investigator of the VISION trial, and lead author of the published results, considers some of the questions about this novel radiopharmaceutical and how it might be adopted in the US. Dr. Sartor also discusses how the VISION trial fits into new prostate-specific membrane antigen (PSMA) research and explores the future of phenotypic theranostics in precision medicine.

TARGETED ONCOLOGY: What are the key takeaways from the VISION trial?

SARTOR: I think there are a couple. No. 1 is [that] we really wanted to design a trial that would result in regulatory approval in multiple countries, so that was the goal starting out. Of course, we wanted to use the PSMA Lu-177 using the PSMA-617 targeting molecule. That was kind of where we started.

I also felt that having prolongation of survival as an end point was key. To meet it, we chose very difficult-to-treat patients. The patients who enrolled in VISION had already gone through chemotherapy and at least 1 taxane. Many of the patientsabout 40%had actually had 2 lines of a taxane chemotherapy prior to enrolling in the trial. Everyone was also required to have use[d] at least 1 novel hormone, but multiple novel hormones were allowed. Abiraterone and enzalutamide, for instance, would have previously been used. A substantial proportion of them had undergone not just 1 but 2 chemotherapies, and all of them had undergone multiple hormonal treatments. These patients were extremely difficult to treat.

We also used the PSMA PET scan to choose and exclude patients. We wanted to choose patients who have PSMA PET metastases greater than just in the liver. This wasn't a stringent criterion, but we wanted to make sure that everybody had PSMA positivity. We also excluded patients who had PSMA negativity, lymph nodes greater than 2.5 cm, or visceral lesions of more than 1 cm.[There] were [also] a variety of other inclusion criteria like adequate performance status, adequate bone marrow, etc.

Included patients were randomized to receive a nonchemotherapeutic standard of care [treatment]. This included additional hormones, radiation therapy, bisphosphonates, maybe steroids plus or minus the PSMA lutetium, etc. There was a 2-to-1 randomization. Overall survival (OS) was an end point. Also, after the trial was already designed, there was a radiographic progression-free survival (rPFS) end point added. Patients were intended to be treated with at least 4 cycles for the PSMA lutetium and could receive up to 6 if there was evidence of clinical benefit. That's the basic framework of the trial.

The bottom line is we hit OS, and we hit rPFS. I think the safety profile was good. We also had health-related quality-of-life improvement for the PSMA lutetium. I believe this trial will result in multiple regulatory approvals, which was the goal that we set out to accomplish.

TARGETED ONCOLOGY: Based on findings from the VISION trial, what might we expect from ongoing clinical trials investigating Lu-PSMA-617 earlier in the natural history of prostate cancer?

SARTOR: Patients in the VISION trial had all failed a novel hormone and a taxane-based chemotherapy, so the VISION trial [included]advanced patient[s] with chemotherapy exposure. However, many patients with prostate cancer never receive chemotherapy, so were now starting a trial for patients with [m]CRPC called PSMAfore (NCT04689828), [which] doesn't require patients prior use of chemotherapy. Here, we're taking patients without chemotherapy exposure, but we're requiring that they have at least abiraterone or enzalutamide as a prior treatment. PSMAfore is moving forward with an rPFS end point with a crossover for those who are on the control arm, [so] they would have the opportunity to also receive PSMA lutetium. That trial is already accruing: I've already personally enrolled patients into the trial.

PSMAfore examines the castration-resistant space. We're also moving into the castration-sensitive space. In a phase 3 trial, we're going to be examining metastatic castrate-sensitive prostate cancer. Everybody receives androgen-deprivation therapy (ADT) and a novel hormone. The novel hormone can be [the] doctor's choice: abiraterone, enzalutamide, or apalutamide, all of which are FDA approved. This trial [is] plus or minus the PSMA lutetium. Here again, we're using an rPFS end point. This is going to be a big global trial. It, too, is already accruing patients. We've already consented our first patient here in the United States, and it's accruing in multiple countries around the globe.

We're hopeful that these earlier stage trials with PSMA-617 lutetium are going to result in more regulatory approvals for less heavily pretreated patients than were present in VISION.

There's also another phase 3 trial called the SPLASH trial (NCT04647526) using a PSMA-targeted radiopharmaceutical. Again, [it is] Lu-177, but this time instead of PSMA-617, it is 177 Lu-PSMA-I&T.

The[re] are additional phase 3 trials in the mCRPC nonchemotherapy-pretreated space. These trials are not quite underway to the same degree that PSMAfore is. Nevertheless, I think they can add value as we move forward.

TARGETED ONCOLOGY: If approved, how might Lu-PSMA fit within the current treatment landscape for mCRPC? What challenges do you anticipate for the use or acceptance of this agent?

SARTOR: I think the first label will be in accordance with the VISION-selected patients: mCRPC by conventional imaging and prior treatment with both a novel hormone such as abiraterone or enzalutamide and at least 1 taxane. Everybody would need to be PSMA-positive on the PET scan in accordance with the criteria that we established in VISION, I anticipate. That might not be the case, but I suspect it will.

After approval, the barriers are going to be severalfold. No. 1, there are going to be a lot of patients who do not want chemotherapy and are not treated with chemotherapy. They're going to be frustrated that they can't get this agent because the FDA and other regulatory bodies, I think, are going to require the chemotherapy pre-treatment. That's going to be 1 issue, [and] that's going to be addressed with PSMAfore and others.

No. 2, there are already access issues in the United States for PSMA PET. Not all of the insurance companies have approved it. If a PSMA PET [scan] is required, then somehow all these PSMA PET scans are going to have to be performed. That's a potential holdup.

No. 3, I think that the specialties that are qualified to administer the radiopharmaceuticalseither nuclear medicine or radiation oncologymay be overwhelmed with the demand. I'm worried that not enough centers are going to be ready. Ideally, these patients should be under multidisciplinary care. These are individuals who have multiple potential complications. It's not just pushing an isotope and seeing the patient back in 6 weeks. Multidisciplinary care is optimal. However, getting these patients through multi-d[isciplinary] clinics [to be sent] to those who are qualified to administer the therapy and then ensuring that theyve had chemotherapy and getting them [PSMA] PET scans could all be a hindrance.

There are stumbling blocks that could be apparent, and I think we're going to have to watchall of these as we go forward.

TARGETED ONCOLOGY: Looking beyond Lu-PSMA and the VISION trial, what do you think is most important for clinicians to emphasize in future efforts to treat patients with advanced prostate cancer effectively?

SARTOR: No. 1, we really need to start multidisciplinary care as soon as possible. Everybody can add value to the patient. If a patient is seeing a radiation oncologist, involving a urologist may be of benefit. If somebody is seeing a urologist, a medical oncologist could be helpful. As we move forward, particularly in these complex cases of patients with multiple areas of metastatic disease, coming together as teams can play an important role.

No. 2, we need to be aware of genetics. There are genetically targeted therapies now available. Folks are aware of the PARP inhibitors for homologous recombination repair defects, but things like pembrolizumab are also important. I mention pembrolizumab by name as a PD-1 inhibitor because this is approved in the context of mismatch repair or microsatellite instability (MSI)-high alterations, or even high tumor mutational burdens. Genetic testing is something I think we need to keep in mind, because sometimes the patients can have very robust responses to targeted therapies, provided they have the appropriate genetic milieu.

No. 3, as we move forward, we have to be cognizant of supportive aspects of our care, such as bone health. We have realized that a lot of patients can have pathogenic fractures and pathologic fractures. Mitigating that risk with things like denosumab or zoledronic acid is an important role for our clinicians to play in the management of patients.

TARGETED ONCOLOGY: What are the most exciting or important areas for researchers in this field to focus on?

SARTOR: Im excited about several areas. No. 1 is combination therapies. Currently, PSMA [Lu]-177 is being evaluated in combination with things like PSMA actinium-225. It's being looked at in combination with DNA repair inhibitors such as the PARP inhibitor olaparib, it's being looked at in combination with the PD-1 inhibitors like pembrolizumab, [and] its being evaluated in combination with stereotactic body radiotherapy. As we move forward, combination therapies are important.

Additional isotopes, combinations of isotopes, bispecific antibodies, and novel hormonal targeting agents that are being developed are also exciting, so there's a lot for us to keep aware of as this field marches forward.

TARGETED ONCOLOGY: PSMA-based radiotracers are the latest in a line of biomarkers used in prostate cancer imaging. Do you foresee other biomarkers becoming relevant? What role might PSMA have alongside them?

SARTOR: Combinations of PET imaging may yield very interesting results. For instance, we're having trouble treating emerging neuroendocrine prostate cancer. Often, after previous treatment with agents like abiraterone and enzalutamide, these neuroendocrine phenotypes emerge. The cell surface markers for neuroendocrine phenotypes may be very interesting. I'll mention the bombesin receptor as one. It turns out that these neuroendocrine tumors express receptors beyond just PSMA.

I think PSMA is a fabulous target, by the way, [but] different ways to image PSMA may also be important. There [are] also image-based biomarkers related to the use of immunotherapy. Being able to image things like PD-L1 [may] also [be] quite important.

As we go forward, Im seeing a whole series of newer PET [bio]markers being evaluated, and utility [may be] growing out of even combinations. The Australians today use 18 F-FDG PET in combination with PSMA PET, and by the way, I think that could potentially add value, but it needs to be properly evaluated in the context of prospective trials.

TARGETED ONCOLOGY: What is on the short-term horizon for research in prostate cancer treatment?

SARTOR: I think the short-term horizon in prostate cancer is going to revolve [around] moving these novel radiopharmaceuticals closer to the front of therapy. I've mentioned several trials, including the SPLASH trial, the PSMAfore trial, and the PSMA addition trial, which is for castration-sensitive [prostate cancer], upfront. All of these are going to be actively accruing subjects. I don't think we'll have results in the next 12 to 18 months, but nevertheless, that's going to be the next chain. In addition, we're going to see the rise of these combination therapies initially in phase 1 moving on to phase 2. And then I think we're going to evolve a whole series of novel biomarkers, and these are going to require additional testing, of course, but the field of biomarkers is alive and well. [It is] evolving so, so rapidly right now.

TARGETED ONCOLOGY: As phenotypic theranostics advance, what might be the role of genotypic precision medicine in prostate cancer? Do you think that these 2 areas will grow alongside one another?

SARTOR: I do. When we talk about precision medicine, I think most [but not all] of what weve become accustomed to is related to the genomic alterations that occur in the context of cancer, but phenotypic alterations such as PSMA expression [are] not going to be something you can detect with a gene rearrangement. Its really about protein expression. I think this area also has a bright future. I mentioned very particularly the expression of neuroendocrine markers. I mentioned the bombesin receptor, which is a gastrin-releasing peptide (GRP) receptor. Maybe somatostatin receptors could be important. Maybe other alterations such as DLL3 could be important. These would be called phenotypic biomarkers as opposed to genotypic biomarkers, which would be things like BRCA2 mutations, mismatch repair, rearrangements, etc.

Precision medicine is going to evolve, I think, on multiple fronts. The beauty of a targeted radiopharmaceutical is that almost anything that you can bind to on the cell surface potentially becomes a target. That means were going to have a vastly expanded series, in my opinion, over the next several decades of targets on cell surfacesnot just for prostate cancer, but for a whole series of different cancers. Right now, we have neuroendocrine cancers of the midgut, the so-called carcinoids, and those neuroendocrine-type cancers that are targeted, but I envision many, many more theranostics going forward, and [LuPSMA] is just a first step.

References

1. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer.N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322

2. FDA grants priority review for investigational targeted radioligand therapy 177Lu-PSMA-617 for patients with metastatic castration-resistant prostate cancer (mCRPC). News release. Novartis. September 28, 2021. Accessed December 9, 2021. https://www.novartis.com/news/fda-grants-priority-review-investigational-targeted-radioligand-therapy-177lu-psma-617-patients-metastatic-castration-resistant-prostate-cancer-mcrpc

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EP. 6B: Phenotypic Theranostics in the Future of Precision Medicine - Targeted Oncology

NEW YORK & SEATTLE--(BUSINESS WIRE)--Emendo Biotherapeutics, a next-generation CRISPR biotech expanding the reach of gene editing therapeutics, and Seattle Childrens Research Institute today announced a research collaboration to investigate how hematopoietic stem cells (HSCs) extracted from patients with severe congenital neutropenia (SCN) respond to priming treatments ahead of administering a CRISPR-based therapeutic.

ELANE-related SCN, also known as SCN1, is a rare, autosomal dominant disease in which a mutation occurs in one allele of the ELANE gene, thereby preventing HSCs from differentiating into white blood cells, specifically neutrophils, which leaves the patient highly susceptible to recurrent bacterial infections, osteoporosis, developmental delays and abnormalities.

Patients with SCN often suffer from reduced quality of life due to the lack of improvements in the standard of care, said Dr. David Rawlings, Division Chief of Immunology at Seattle Children's Hospital and Director of the Center for Immunity and Immunotherapies at Seattle Childrens Research Institute. These children are immunocompromised, and, as a result, we feel a great sense of urgency to ensure were exploring all possible avenues towards a solution.

Seattle Childrens collaboration with Emendo, utilizing its unique approach to edit only the mutated allele with CRISPR, will enable us to address the unmet needs of SCN at the very core, added Rawlings, who also serves as a professor of pediatrics and adjunct professor in the Department of Immunology at the University of Washington School of Medicine. Were excited about this opportunity, and look forward to continuing the collaboration beyond this initial study.

Editing the mutated ELANE gene with CRISPR first requires overcoming a technological hurdle: Only the mutated allele must be targeted, while the healthy allele remains intact. Emendo engineered its roster of next-generation CRISPR nucleases to be biologically active and so specific that they can differentiate between two alleles of the same gene. EMD-101, Emendos lead therapeutic candidate for SCN, was specifically engineered to target the mutant ELANE allele.

HSCs have been widely studied as a treatment for sickle cell anemia and cancer, as well as a potential therapy to treat organ and tissue damage. However, HSCs require initial priming prior to stem cell transplantation, which is typically done by administering G-CSF (granulocyte colony stimulating factor). Yet, the same drug is also a short-term treatment for SCN patients.

To better understand how SCN patients would respond to a priming dose of G-CSF and plerixafor, Emendo will evaluate the mobilization of HSCs excised from a small group of patients with SCN, which would be gene-edited later. Concurrently, Seattle Childrens will evaluate the composition of the HSCs obtained from the same patients. Prior mouse studies conducted by Emendo have shown that human cells edited to excise the disease-causing ELANE allele sufficiently engrafted and replaced existing diseased cells, restoring proper neutrophil differentiation.

By combining our allele-specific genome editing technology with Seattle Childrens renowned expertise in SCN spearheaded by Dr. Rawlings we are laying the foundation for future clinical trials that could lead to potential therapies to treat the disease, said David Baram, Ph.D., CEO of Emendo. Our portfolio of engineered nucleases tailored to any gene or allele gives us the unique opportunity to tackle the inherent challenges of SCN. Through this collaboration well be able to provide stronger evidence and further proof points for the capabilities of our technology.

Based on the outcome of the research, a protocol for a clinical trial could be developed with an expected initiation in late 2022, pending regulatory approval. Seattle Children's has certain preferred rights to serve as a clinical trial site.

About Emendo Biotherapeutics

EmendoBio is a next generation CRISPR gene editing company leveraging dual proprietary technology platforms to enable high precision gene editing throughout the genome. EmendoBios novel nuclease discovery platform broadens the targetable range of the genome while its target-specific optimization platform enables highly precise editing, including allele specific editing, while maintaining high efficiencies. The capabilities of the OMNI technology platforms, along with deep expertise in genomic medicine, protein engineering and therapeutic development, provide EmendoBio with a unique advantage when addressing indications within hematology, oncology, ophthalmology and other disease areas. For more information please visit us at http://www.emendobio.com.

About Seattle Childrens

Seattle Childrens mission is to provide hope, care and cures to help every child live the healthiest and most fulfilling life possible. Together, Seattle Childrens Hospital, Research Institute and Foundation deliver superior patient care, identify new discoveries and treatments through pediatric research, and raise funds to create better futures for patients.

Ranked as one of the top childrens hospitals in the country by U.S. News & World Report, Seattle Childrens serves as the pediatric and adolescent academic medical center for Washington, Alaska, Montana and Idaho the largest region of any childrens hospital in the country. As one of the nations top five pediatric research centers, Seattle Childrens Research Institute is internationally recognized for its work in neurosciences, immunology, cancer, infectious disease, injury prevention and much more. Seattle Childrens Foundation works with the Seattle Childrens Guild Association, the largest all-volunteer fundraising network for any hospital in the country, to gather community support and raise funds for uncompensated care and research. Join Seattle Childrens bold initiative It Starts With Yes: The Campaign for Seattle Childrens to transform childrens health for generations to come.

For more information, visit seattlechildrens.org or follow us on Twitter, Facebook, Instagram or on our On the Pulse blog.

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Emendo Biotherapeutics and Seattle Children's Research Institute Announce Collaboration to Develop CRISPR-based Therapeutic Strategy for Severe...

We, the medical and clinical-administrative directors of the Optilab laboratory medicine clusters in Quebec, sincerely thank you for your hard work and dedication. In the extremely challenging context of COVID-19 for laboratory personnel, you put all your expertise and energy into serving Quebecers every day to provide reliable laboratory analyses that are essential to care.

Thanks to you, millions of molecular virology COVID screening tests have been performed in microbiology departments. Your work has enabled the development of sophisticated new assays using next generation gene sequencing in the molecular genetics departments. These analyses are now available to the Quebec population for personalized cancer medicine. Thanks to you, thousands of detailed examination of tissue and their characteristics, on which most treatment decisions depend, are made every day in the pathology services. In addition, sophisticated coagulation analyses are made in hematology services for the management of people with hemophilia and high-throughput tests of pharmacological molecules are completed in biochemistry services. Furthermore, through the analyses performed in the transfusion medicine departments, you allow decisions to be made that are sometimes vital in emergency situations.

These examples represent a small fraction of the procedures performed every day in the clinical laboratories of Quebec hospitals. None of this would be possible without you. You are this network and we are immensely proud and honored to work alongside you.

We thank you for all the work you do in the laboratories of Quebec hospitals, for your willingness and your talent. We wish you and your loved ones happy holidays and a Happy New Year!

Dany Aubry, Ren Bergeron, Mlanie Bernard, Normand Brassard, Enzo Caprio, Dr. Christian Carrier, Martin Coulombe, Dr. Jean-Franois Dermine, Dr. Jean Dub, Dr. Linda Lalancette, Bruno Lamontagne, Dr. Emmanuelle Lemyre, Dr. Franois Lessard, Andr Lortie, Dr. Daniele Marceau, Zied Ouechteti, Dr. Jean-Franois Paradis, Genevive Plante, Annie Robitaille, Dr. Benot Samson, Dr. Alan Spatz, Sylvie Thibeault, Sophie Verdon, Dr. Andr Vincent, Dr. Ewa Barbara Wesolowska

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Open letter to employees, technologists, professionals and physicians of the Optilab laboratory medicine clusters in Quebec - McGill University Health...