Category Archives: Genetic medicine

The June 24 decision by the Supreme Court to overturn Roe v. Wade struck close to home for genetic counselors, the medical professionals who are often tasked with advising and consoling prospective parents when ultrasounds or other prenatal tests indicate a threat to their own health or the health of their future child. People seeking abortions based on health concerns during pregnancy are a small percentage of abortion seekers overall, but they are disproportionately affected by the new barrage of restrictions because detecting and confirming a prenatal diagnosis takes time. The abortion drug mifepristone is approved for use by the Food and Drug Administration only through the 10th week of pregnancywell before patients receive the results of genetic testing or anatomy scans. Patients are also likely to find themselves in a bind because of state restrictions on how far along a pregnancy can be when an abortion takes place.

Prenatal counselors must now work around the need for patients to travel out of state for abortion careand somehow try to help patients without the financial means to make these trips. The disparity of access is likely to exacerbate existing health risks associated with being poor and pregnant. Im very worried about maternal mortality, says genetic counselor Shannon Barringer. She has worked for 25 years in the state of Arkansas, where a trigger law that went into effect on June 24 has made abortion illegal even in cases where the fetus is not expected to survive. Barringer also worries that new legislation may make it harder for her to provide that help. I know [legislators are] already working with national organizations to draft language that may interfere with health providers being able to refer out of state, she says.

In fact, existing and proposed laws restricting abortion have become so extreme that they are likely to affect all prenatal patients, not just those who need an abortion. In a recent series of interviews conducted by two graduate students at Sarah Lawrence College, prenatal genetic counselors practicing in states hostile to abortion said that the need to send patients out of state if they were to need an abortion created time pressure that affected many aspects of prenatal care. (The author of this article teaches at Sarah Lawrence.) Some counselors reported that they were rescheduling detailed anatomy scans, typically done between the 20th and 22nd week of pregnancy, to be carried out at 18 or even 16 weeks, despite evidence that earlier scans will miss some fetal anomalies and give less definitive information on others.

A fuller picture of the effect on genetic counseling can be seen in Texas, where these services have operated in a de facto post-Roe world since September 2021, when a law went into effect making all but the earliest abortions illegal. That same law also permits any citizen so inclined to sue anyone aiding or abetting an illegal abortion for a sum up to $10,000. While few of these vigilante suits have reached the courts, the law has succeeded in creating an atmosphere of fear and suspicion. In fact, all four genetic counselors from Texas interviewed by Scientific American for this article said that their institutions required them to speak anonymously. Ive tried consciously, since the law passed, to make the counseling session a safe place for people to go, says one counselor working in Houston. But on the flip side of that, I wonder if I or my genetic counseling colleagues are opening ourselves up for potential lawsuits.

This tension between optimal patient care and self-preservation is not likely to improve anytime soon. New proposals directly target the ability of health professionals to provide guidance to their patients. A bill recently introduced in the South Carolina legislature would make it a felony, with mandatory prison time, to offer information to anyone attempting to obtain an abortion, even if one only directs that person to a Web site. With the threat of legal jeopardy, some genetic counselors may be deterred from even engaging in routine conversations that help determine which types of prenatal tests are best for an individual patient because they could be perceived as raising the question of whether or not that patient wants the option of terminating a pregnancy.

Concerns about liability have also raised questions about whether to limit what information goes into a medical record. Weve debated it, says another Houston counselor. Certain people in our department feel strongly that documentation of a legal procedure out of state should be in the chart so that the patient can get the best possible care, whereas other doctors will say..., Why not avoid that language and just kind of be, you know, abstract about it?

A recent JAMA Health Forum editorial by law professors Kayte Spector-Bagdady and Michelle Mello argues forcefully that medical providers should be aware that not only medical records but their own e-mails may be used by law enforcement officials prosecuting abortion. Doctors are not the only ones who are fearful. Barringer says that because of the current uncertainties, patients do not want details about past pregnancies documented or will not provide her with that information. Barringer adds that she sympathizes with their concerns but worries a lack of medical history could interfere with providing the safest care possible in a future pregnancy.

Already, Barringer says, patients are concerned about sharing information on use of pills that induce an abortionwith or without a prescriptionbecause of the Arkansas law that criminalizes harm to the fetus. New abortion restrictions that include language establishing fetal rights or fetal personhood will exacerbate existing disincentives to open communication. Michele Goodwin, a law professor at the University of California, Irvine, argues in her 2020 book Policing the Womb that there is increasing jeopardy for any pregnant person but particularly for those of color, who have historically been the target of prosecutorial overreach. With both genetic counselors and patients worried about what is safe to say, it will be harder than ever to establish the atmosphere of trust that is a bedrock of good medicine.

Anecdotally, says a Texas genetic counselor, Ive already noticed some patients not wanting to fill out the intake form for pregnancies. And Ive had people share things verbally they dont want to put in the paperwork. Not having the information impedes her ability to do her job. This might mean not knowing about an exposure to a drug, legal or illegal, that could affect fetal development. It might mean not learning about a previous pregnancy that ended in a miscarriage or abortion related to fetal health and therefore being unable to address the risk of the problem recurring.

Another genetic counselor mentions that in one recent case, a prenatal patient with abnormal ultrasound findings came to believe that the problems could have been caused by an abortion she had failed to disclose when she gave her medical history. Only after the patient felt comfortable enough to confide in her could the counselor correct the womans misapprehensions and address her emotional needs. She wanted to know if she caused this, the counselor says. She had a lot of shame and guilt.

As attacks on access to abortion proliferate, genetic counselors worry that prenatal testing itself may become harder to access. Tests such as noninvasive prenatal testing (NIPT), which examines snippets of fetal DNA floating in the maternal bloodstream for missing or added DNA, are extremely popular with patients. But they can be seen as a stepping stone to abortion. In 2012 Republican presidential aspirant Rick Santorum was widely ignored when he said that health insurance companies should not be required to pay for amniocentesis because it was often used to encourage abortion. Ten years later Santorums position, while extreme, now must be taken seriously. I can see that potentially being a problem, Barringer says, noting that Arkansas, like many other states, already prohibits insurance companies from offering policies that cover termination of pregnancy.

Restricting the use of expensive prenatal genetic testing to those who can pay for it out of pocket would effectively implement a lower standard of prenatal care for those who live in abortion-hostile states. Some would lose the opportunity to prevent the birth of a child with a genetic condition. Otherswho would not have terminatedlose the chance to prepare for the birth of a child with special needs and to avoid a long and often arduous search for a diagnosis as evidence of a problem emerges postnatally.

Even for those who can afford it, prenatal genetic counseling may become increasingly hard to find. All four genetic counselors from Texas spoke movingly of an obligation to serve their patients, coupled with the strain of working in an environment in which they could not help them as they once did. In one e-mail to Scientific American, a counselor from Dallas wrote that she worried for days about not providing information to a patient who asked for guidance on finding an abortion clinic out of state before deciding to share what she called a minute amount of information. And then she worried for days afterward about whether what I had said could be construed as aiding or abetting.

Genetic counseling is a limited resource. In a fast growing field, demand continues to outstrip supply. Going forward, it may be hard to find candidates for positions whose fringe benefitsinclude extra emotional burdens and potential legal liability. Barringer, contemplating laws that might restrict her ability to counsel patients as she has done for 25 years, is reluctantly considering what it would mean to turn away from a job she loves. Its making me think, If that comes to fruition here, I dont know if, ethically, Ill be able to continue. If I couldnt help my patients through some of the worst things that human beings can go through..., I honestly dont know what I would do.

Go here to read the rest:
Genetic Counselors Scramble Post- Roe to Provide Routine Pregnancy Services without Being Accused of a Crime - Scientific American

The following discussion and analysis of our financial condition and results ofoperations are meant to provide material information relevant to an assessmentof the financial condition and results of operations of our company, includingan evaluation of the amounts and uncertainties of cash flows from operations andfrom outside resources, so as to allow investors to better view our company frommanagement's perspective. It should be read in conjunction with our condensedconsolidated financial statements and related notes appearing elsewhere in thisQuarterly Report on Form 10-Q, or Quarterly Report, and our consolidatedfinancial statements and related notes appearing in our most recently filedAnnual Report on Form 10-K, or Annual Report, with the Securities and ExchangeCommission, or SEC. Some of the information contained in this discussion andanalysis or set forth elsewhere in this Quarterly Report, including informationwith respect to our plans and strategy for our business, includesforward-looking statements that involve risks and uncertainties. As a result ofmany factors, including those factors set forth in the "Risk Factors" section ofthis Quarterly Report, in our Annual Report and in the other documents filedwith the SEC, our actual results could differ materially from the resultsdescribed in, or implied by, the forward-looking statements contained in thefollowing discussion and analysis.

Overview

Furthermore, we plan to expand our portfolio to include rare and prevalentdiseases of the skeletal muscle, the central nervous system and oncology bydeveloping discrete ctLNPs, each engineered to reach a different tissue.

? obtain, expand, maintain, defend and enforce our intellectual property

portfolio;

? continue our current research programs and conduct additional research

programs;

? expand the capabilities of our proprietary non-viral genetic medicine platform;

add operational, legal, compliance, financial and management information? systems and personnel to support our research, product development, future

commercialization efforts and operations as a public company;

develop our capabilities to manufacture and establish additional commercial? manufacturing sources and secure supply chain capacity sufficient to provide

necessary quantities of any product candidates we may develop for clinical or

commercial use;

? hire additional clinical, regulatory and scientific personnel;

? advance any product candidates we identify into preclinical and clinical

development;

? seek marketing approvals for any product candidates that successfully complete

clinical trials; and

? ultimately establish a sales, marketing and distribution infrastructure to

commercialize any products for which we may obtain marketing approval.

Table of Contents

support product sales, marketing and distribution. Further, we expect tocontinue to incur additional costs associated with operating as a publiccompany.

COVID-19

We expect to continue to take actions as may be required or recommended bygovernment authorities or as we determine are in the best interests of ouremployees and other business partners in light of the pandemic.

Table of Contents

Components of Our Results of Operations

Operating expenses

Research and development expenses

personnel-related costs, including salaries, benefits and stock-based? compensation expense, for employees engaged in research and development

functions;

expenses incurred in connection with our research programs, including under? agreements with third parties, such as consultants, contractors and CROs, and

regulatory agency fees;

the cost of developing and scaling our manufacturing process and capabilities? and manufacturing drug substance and drug product for use in our research and

preclinical studies, including under agreements with third parties, such as

consultants, contractors and CMOs;

? laboratory supplies and research materials;

facilities, depreciation and amortization and other expenses, which include? direct and allocated expenses for rent and maintenance of facilities and

insurance; and

? payments made under third-party licensing agreements.

? the timing and progress of preclinical studies, including investigational new

drug, or IND , -enabling studies;

? the number and scope of preclinical and clinical programs we decide to pursue;

? raising additional funds necessary to complete preclinical and clinical

development of our product candidates;

the timing of the submission and acceptance of IND applications or comparable? foreign applications that allow commencement of future clinical trials for our

product candidates;

? the successful initiation, enrollment and completion of clinical trials,

including under Good Clinical Practices;

our ability to achieve positive results from our future clinical programs that? support a finding of safety and effectiveness and an acceptable risk-benefit

profile in the intended patient populations of any product candidates we may

develop;

? our ability to scale RES to produce clinical and initial commercial supply;

? our ability to establish arrangements with third-party manufacturers for

preclinical and clinical supply;

? the availability of specialty raw materials for use in production of our

product candidates;

? our ability to establish new licensing or collaboration arrangements;

? the receipt and related terms of regulatory approvals from the U.S. Food and

Drug Administration and other applicable regulatory authorities;

our ability to establish, obtain, maintain, enforce and defend patent,? trademark, trade secret protection and other intellectual property rights or

regulatory exclusivity for any product candidates we may develop and our

technology; and

? our ability to maintain a continued acceptable safety, tolerability and

efficacy profile of our product candidates following approval.

General and administrative expenses

Other income and interest income

Other income and interest income consists of interest income earned on ourinvested cash balances and other miscellaneous income unrelated to our coreoperations.

Comparison of the three and six months ended June 30, 2022 and 2021

The following table summarizes our results of operations for the three andsix months ended June 30, 2022 and 2021:

(7,639) (73,825) (56,497) (17,328)Other income:Other income and interest income

Research and development expenses

The following table summarizes our research and development expenses for thethree and six months ended June 30, 2022 and 2021:

5,767 $ 1,656 $ 15,169 $ 11,155 $ 4,014Preclinical and manufacturing

920

Total research and development expenses $ 28,365 $ 22,656 $ 5,709 $ 53,919 $ 41,409 $ 12,510

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General and administrative expenses

The following table summarizes our general and administrative expenses for thethree and six months ended June 30, 2022 and 2021:

2,547

Total general and administrative expenses $ 10,116 $ 8,186 $ 1,930 $ 19,906

4,818

Other income and interest income

Liquidity and Capital Resources

3,593 213,930Net increase in cash, cash equivalents and restricted cash $ (216,880) $ 329,183

Investing activities

Financing activities

? the identification of additional research programs and product candidates;

? the scope, progress, costs and results of preclinical and clinical development

for any product candidates we may develop;

? the costs, timing and outcome of regulatory review of any product candidates we

may develop;

? the cost and timing of clinical and commercial-scale manufacturing activities;

the costs and timing of future commercialization activities, including product

? manufacturing, marketing, sales and distribution, for any product candidates we

may develop for which we receive marketing approval;

? the costs and scope of the continued development of our non-viral genetic

medicine platform;

? the costs of satisfying any post-marketing requirements;

? the revenue, if any, received from commercial sales of product candidates we

may develop for which we receive marketing approval;

Excerpt from:
GENERATION BIO CO. Management's Discussion and Analysis of Financial Condition and Results of Operations. (form 10-Q) - Marketscreener.com

Conference Call and Webcast Scheduled for 4:30 p.m. Eastern Time

BRISBANE, Calif., August 04, 2022--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, today reported recent business highlights and second quarter 2022 financial results.

"We made meaningful progress advancing our clinical-stage programs in the second quarter," said Sandy Macrae, Chief Executive Officer of Sangamo. "We are engaging in pivotal study-enabling activities in two of our clinical stage programs and are preparing to complete dosing of the first cohort in our TX200 program, which recently received Orphan Medicinal Product Designation from the European Commission. Coupled with strong advances in our preclinical pipeline, we believe this progress positions us well to advance the development of potentially transformational genomic medicines for patients in need and to generate long-term value for our shareholders."

Recent Business Highlights

Fabry disease Received endorsement to progress into the Ph1/2 studys expansion phase; continued to recruit patients and activate sites; Phase 3 planning progresses.

In June, the Safety Monitoring Committee endorsed progressing the Phase 1/2 STAAR study evaluating isaralgagene civaparvovec, our wholly owned gene therapy product candidate for the treatment of Fabry disease, from the dose escalation phase into the expansion phase at the dose level of 5e13 vg/kg.

We expect to dose two additional patients imminently, and have multiple patients in screening, including both male and female candidates.

Enzyme replacement therapy (ERT) withdrawal was completed for an additional two patients previously dosed in the STAAR study, achieving a total of four patients to date who have successfully been withdrawn.

A total of 16 study sites are now open and recruiting, including the first sites in Canada, Italy and Australia.

We plan to provide updated results from the STAAR study in the second half of 2022, including at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium, taking place August 30-September 2, 2022.

We continue to actively prepare for a potential pivotal Phase 3 trial.

Story continues

Sickle cell disease Completed transition of program back to Sangamo; advanced manufacturing activities in anticipation of dosing in Q3; Phase 3 planning progresses.

We completed the transition of Sanofis rights and obligations under the collaboration developing BIVV003, formerly known as SAR445136, our zinc finger nuclease gene-edited cell therapy candidate for the treatment of sickle cell disease, back to Sangamo on June 28, 2022.

Manufacturing of product candidates using improved methods progressed in the Phase 1/2 study. These improved manufacturing methods have been shown in internal experiments to increase the number of long-term progenitor cells in the final product.

Dosing of the next patient is anticipated in the third quarter of 2022.

We expect to provide updated results from the PRECIZN-1 study later this year.

Phase 3 enabling activities and manufacturing readiness are in progress.

Hemophilia A Pfizer advised us that it continues to expect resumption of dosing in Q3 2022; pivotal data read-out expected in late 2023 or early 2024.

Pfizer advised us that it continues to anticipate resuming the dosing of additional patients in the Phase 3 AFFINE trial of giroctocogene fitelparvovec, an investigational gene therapy we are developing with Pfizer for patients with moderately severe to severe hemophilia A, in the third quarter of 2022.

A pivotal data readout is estimated in late 2023 or early 2024.

Over 50% of the patients have been enrolled in the Phase 3 AFFINE trial.

Renal Transplant Rejection Received Orphan Medicinal Product Designation from the European Commission; progressed manufacturing and clinical activities ahead of anticipated Q3 dosing.

Since we dosed the first patient in the Phase 1/2 STEADFAST study evaluating TX200, our wholly owned autologous CAR-Treg cell therapy treating patients receiving an HLA-A2 mismatched kidney from a living donor, the product candidate continues to be generally well tolerated, with no treatment related adverse events.

We completed manufacturing of the dose for the second patient, who recently received a kidney transplant. Dosing of this second patient is expected later in the third quarter of 2022.

We plan to complete dosing of the first cohort, comprised of three patients, by the end of 2022.

The European Commission granted Orphan Medicinal Product Designation to TX200, for treatment in solid organ transplantation, following a positive opinion from the European Medicines Agencys Committee for Orphan Medicinal Products.

American Society of Gene and Cell Therapy (ASGCT) Profiled significant pre-clinical progress across Sangamos innovative pipeline and platform.

Presented seven posters and one oral presentation at ASGCT on May 16-19, 2022, including pre-clinical updates across our CAR-Treg autoimmune cell therapy platform, innovations in our genome engineering platform and advances in our AAV capsid engineering program.

Second Quarter 2022 Financial Results

Consolidated net loss for the second quarter ended June 30, 2022, was $43.2 million, or $0.29 per share, compared to a net loss of $47.2 million, or $0.33 per share, for the same period in 2021.

Revenues

Revenues for the second quarter ended June 30, 2022, were $29.4 million, compared to $27.9 million for the same period in 2021.

The increase of $1.5 million in revenues was primarily attributed to an increase of $1.3 million in revenue related to our collaboration agreement with Novartis and an increase of $0.8 million in revenue related to our collaboration agreement with Sanofi. These increases were partially offset by a decrease of $0.7 million in revenue related to our collaboration agreement with Biogen.

GAAP and Non-GAAP operating expenses

Three Months Ended

Six Months Ended

June 30,

June 30,

(In millions)

2022

2021

2022

2021

Research and development

$

60.0

$

60.1

$

118.6

$

116.6

General and administrative

15.1

16.5

30.0

32.6

Total operating expenses

75.1

76.6

148.6

149.2

Stock-based compensation expense

(7.9

)

(9.5

)

(15.6

)

(17.1

)

Non-GAAP operating expenses

$

67.2

$

67.1

$

133.0

$

132.1

Total operating expenses on a GAAP basis for the second quarter ended June 30, 2022, were $75.1 million, compared to $76.6 million for the same period in 2021. Non-GAAP operating expenses, which exclude stock-based compensation expense, for the second quarter ended June 30, 2022, were $67.2 million, compared to $67.1 million for the same period in 2021.

The decrease in total operating expenses on a GAAP basis was primarily due to the timing of certain research and development activities.

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of June 30, 2022, were $363.7 million, compared to $464.7 million as of December 31, 2021. Since the beginning of the second quarter, we have raised approximately $43.1 million in net proceeds under our previously announced at the market offering program.

Financial Guidance for 2022 Reiterated (initial guidance provided on February 24, 2022)

On a GAAP basis, we continue to expect total operating expenses in the range of approximately $320 million to $350 million in 2022, which includes non-cash stock-based compensation expense.

We continue to expect non-GAAP total operating expenses, excluding estimated non-cash stock-based compensation expense of approximately $40 million, in the range of approximately $280 million to $310 million in 2022.

Upcoming Events

Sangamo plans to participate in the following events in the third quarter:

Scientific / Medical Conferences

Society for the Study of Inborn Errors of Metabolism (SSIEM), August 30-September 2, 2022, Freiburg, Germany

Prion 2022, September 13-16, 2022, Gottingen, Germany

Investor Conferences

Wedbush PacGrow Healthcare Conference, August 9-10, 2022 [9:10-9:40am EDT]

H.C. Wainwright 24th Annual Global Investment Conference, September 12-14, 2022

Jefferies Cell and Genetic Medicine Summit, September 29-30, 2022

Access links for these investor conferences will be available on the Sangamo Therapeutics website in the Investors and Media section under Events and Presentations. Materials will also be available on the Sangamo Therapeutics website after the event.

Conference Call to Discuss Second Quarter 2022 Results

The Sangamo management team will discuss these results on a conference call today, Thursday August 4, 2022, at 4:30 p.m. Eastern Time.

Read more:
Sangamo Therapeutics Reports Recent Business Highlights and Second Quarter 2022 Financial Results - Yahoo Finance

A fruit fly genome is not a just made up of fruit fly DNA at least for one fruit fly species. New research from the University of Maryland School of Medicines (UMSOM) Institute for Genome Sciences (IGS) shows that one fruit fly species contains whole genomes of a kind of bacteria, making this finding the largest bacteria-to-animal transfer of genetic material ever discovered. The new research also sheds light on how this happens.

The IGS researchers, led by Julie Dunning Hotopp, PhD, Professor of Microbiology and Immunology at UMSOM and IGS, used new genetic long-read sequencing technology to show how genes from the bacteria Wolbachia incorporated themselves into the fly genome up to 8,000 years ago.

The researchers say their findings show that unlike Darwins finches or Mendels peas, genetic variation isnt always small, incremental, and predictable.

Scientist Barbara McClintock first identified jumping genes in the 1940s like those that can move around within or transfer into other species genomes. However, researchers continue to discover their significance in evolution and health.

We did not have the technology previously to unequivocally demonstrate these genomes-inside-genomes showing such extensive lateral gene transfer from the bacteria to the fly, explained Dr. Dunning Hotopp. We used state-of-the-art long-read genetic sequencing to make this important discovery.

The new research has been published in the June issue of Current Biology.

In the past, researchers had to break DNA into short pieces in order to sequence it. Then they needed to assemble them, like a jigsaw puzzle, to look at a gene or section of DNA. Long-read sequencing, however, allows for sequences more than 100,000 DNA letters, turning a million-piece jigsaw puzzle into one made for toddlers.

In addition to the long reads, the researchers validated junctions between integrated bacteria genes and the host fruit fly genome. To determine if the bacteria genes were functional and not just DNA fossils, the researchers sequenced the RNA from fruit flies specifically looking for copies of RNA that were created from templates of the inserted bacterial DNA. They showed the bacteria genes were encoded into RNA and were edited and rearranged into newly modified sequences indicating that the genetic material is functional.

An analysis of these unique sequences revealed that the bacteria DNA integrated into the fruit fly genome in the last 8,000 yearsexclusively within chromosome 4expanding the chromosome size by making up about 20 percent chromosome 4. Whole bacterial genome integration supports a DNA-based rather than an RNA-based mechanism of integration.

Dr. Dunning Hotopp and colleagues found a full bacterial genome of the common bacteria Wolbachia transferred into the genome of the fruit fly Drosophila ananassae. They also found nearly a complete second genome and much more with almost 10 copies of some bacterial genome regions.

There always have been some skeptics about lateral gene transfer, but our research clearly demonstrates for the first time the mechanism of integration of Wolbachia DNA into this fruit flys genome, Dr. Dunning Hotopp said.

This new research shows basic science at its best, said Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, the John Z. and Akiko K. Bowers Distinguished Professor, and Dean, University of Maryland School of Medicine.It will make a contribution to our understanding of evolution and may even prove to help us understand how microbes contribute to human health.

Wolbachia is an intracellular bacteria that infects numerous types of insects. Wolbachia transmits its genes maternally through female egg cells. Some research has showed that these infections are more mutualistic than parasitic, giving insects advantages, such as resistance to certain viruses.

Sequenced just three years before the human genome, fruit flies have long been used in genomic research because of the abundance of common fly-human genetic similarities. In fact, 75 percent of genes causing human disease can also be found in the fruit fly.

Authors from the Institute of Genome Sciences, University of Maryland School of Medicine, at the time of writing, include Eric S. Tvedte; Mark Gasser; Xuechu Zhao, Lab Research Specialist; Luke J. Tallon, Executive Scientific Director, Maryland Genomics; Lisa Sadzewicz, Executive Director, Maryland Genomics Administration; Robin E. Bromley, Lab Research Supervisor; Matthew Chung; John Mattick, PostDoc, and Benjamin C. Sparklin.

Eric S. Tvedte is currently affiliated with NCBI at the National Institutes of Health, Bethesda, MD; Mark Gasser is currently affiliated with Applied Physics Laboratory, Johns Hopkins University, Laurel, MD; Matthew Chung is currently affiliated with the National Institute for Allergy and Infectious Disease at the National Institutes of Health, Bethesda, MD; and Benjamin C. Sparkin is currently affiliated with AstraZeneca, Rockville, MD.

This work was supported byNational Institute of Allergy and Infectious DiseasesgrantU19AI110820andNational Institutes of HealthgrantR01CA206188.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States.It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicineand the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (University of Maryland Medicine) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8thhighest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visitmedschool.umaryland.edu

About the Institute for Genome Sciences: The Institute for Genome Sciences (IGS) at the University of Maryland School of Medicine has revolutionized genomic discoveries in medicine, agriculture, environmental science, and biodefense since its founding in 2007. IGS investigators research areas of genomics and the microbiome to better understand health and disease, including treatments, cures, and prevention. IGS investigators also lead the development of the new field of microbial forensics. IGS is a leading center for major biological initiatives currently underway including the NIH-fundedHuman Microbiome Project(HMP) and the NIAID-sponsoredGenomic Sequencing Center for Infectious Diseases(GSCID). Follow us on Twitter @GenomeScience.

Experimental study

Animals

Researchers Discover One of the Largest Known Bacteria-to-Animal Gene Transfer Inside a Fruit Fly

20-Jun-2022

The Authors Have No Conflicts of Interest.

See the article here:
Researchers discover one of the largest known bacteria-to-animal gene transfer inside a fruit fly - EurekAlert

Intellia Therapeutics, Inc.

Completed dose-escalation portion of the ongoing Phase 1 study of NTLA-2001 in patients with transthyretin (ATTR) amyloidosis with cardiomyopathy; expects to present interim safety and serum TTR reduction data in 2H 2022

Presented updated interim data from the dose-escalation portion of the polyneuropathy arm, establishing deep reductions of disease-causing protein were sustained through 12 months following a single dose of NTLA-2001

Plans to present interim data for second in vivo CRISPR clinical candidate, NTLA-2002 for hereditary angioedema (HAE), in 2H 2022

Moves to exclusively develop cell therapies leveraging its proprietary allogeneic platform; pivoting to an allogeneic version of NTLA-5001

Ended the second quarter of 2022 with strong cash position of $907 million

CAMBRIDGE, Mass., Aug. 04, 2022 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, today reported operational highlights and financial results for the second quarter ended June 30, 2022.

We continue to make excellent progress in both the cardiomyopathy and polyneuropathy arms of the landmark Phase 1 study of NTLA-2001, said Intellia President and Chief Executive Officer John Leonard, M.D. In June, we presented durability data demonstrating deep reductions in a disease-causing protein were sustained over time following a single-dose treatment. Additionally, weve completed the dose-escalation portion of the cardiomyopathy arm and look forward to starting the dose-expansion portion soon.

Dr. Leonard continued, As the leading full-spectrum genome editing company, our ex vivo capabilities and platform are also advancing. We believe our proprietary, differentiated cell engineering platform can solve many of the known challenges faced by both autologous and current allogeneic approaches. As a result, we plan to focus exclusively on developing allogeneic cell therapies, including an allogeneic version of NTLA-5001. Finally, we expect several important milestones later this year, which will include interim clinical data updates from the NTLA-2001 and NTLA-2002 programs.

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Second Quarter 2022 and Recent Operational Highlights

In Vivo Program Updates

Transthyretin (ATTR) Amyloidosis

NTLA-2001: NTLA-2001 is the first investigational CRISPR-based therapy to be systemically delivered to edit genes inside the human body and has the potential to be the first single-dose treatment for ATTR amyloidosis. Delivered with the Companys in vivo lipid nanoparticle (LNP) technology, NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, potentially lifelong reduction in transthyretin (TTR) protein after a single dose. NTLA-2001 is being evaluated in a Phase 1, two-part, open-label study in adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM). NTLA-2001 is subject to a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc.

To date, over 30 patients have been dosed across the polyneuropathy and cardiomyopathy arms. The growing body of data, particularly at therapeutically relevant doses, demonstrated treatment with NTLA-2001 resulted in rapid, deep and consistent reductions of serum TTR.

ATTR-CM arm: Intellia announced today the completion of the dose-escalation portion of the cardiomyopathy arm. The Company is finalizing selection of a fixed dose, at or near the fixed-dose equivalent of the 0.7 mg/kg dose, for evaluation in the dose-expansion portion of the study, subject to regulatory approval. The selection is based on clinical data from patients with ATTR-CM dosed at the 0.7 mg/kg and 1.0 mg/kg doses, which yielded similar TTR reductions. Additionally, both doses were generally well-tolerated. The Company remains on track to present interim data from the cardiomyopathy arm later this year.

ATTRv-PN arm: The Company announced today, subject to regulatory approval, plans to add a second cohort to the dose-expansion portion of the polyneuropathy arm, which will evaluate the same fixed dose selected for the dose-expansion portion of the cardiomyopathy arm. The decision to study a second dose is based on the following: (1) the emerging data from the dose-escalation portion of the cardiomyopathy arm showed similar serum TTR reduction at both the 0.7 mg/kg and 1.0 mg/kg doses, (2) the comparability of performance at the 0.7 mg/kg and 1.0 mg/kg doses in the dose-escalation portion of the polyneuropathy arm, which led to an 86% and 93% mean and 97% and 98% maximum TTR reduction at day 28, respectively, and (3) a significant elevation in liver enzymes, which normalized without medical intervention, observed at day 28 in a patient treated in the dose-expansion portion of the polyneuropathy arm at the 80 mg dose (the fixed dose corresponding to 1.0 mg/kg). While the adverse event is considered possibly related to study drug, this patient was asymptomatic, had no increase in bilirubin and the event was deemed nonserious by the investigator.

Intellia plans to submit a protocol amendment to evaluate a fixed dose corresponding to 0.7 mg/kg in the dose-expansion portion, with enrollment across both arms expected to be completed by the end of 2022, subject to regulatory feedback.

In June, Intellia presented updated interim data from its ongoing Phase 1 study of NTLA-2001 in patients with ATTRv-PN at the European Association for the Study of the Liver International Liver Congress 2022. Extended follow-up data from 15 ATTRv-PN patients, treated across all four single-ascending dose cohorts, showed deep, dose-dependent reductions in serum TTR observed with prior readouts were sustained through the last measured timepoint of follow-up, reaching 12 months in the 0.1 mg/kg and 0.3 mg/kg cohorts and six months in the 0.7 mg/kg and 1.0 mg/kg cohorts. Both 0.7 mg/kg and 1.0 mg/kg doses led to greater than 85% mean TTR reduction at day 28. The durability and persistence of effect continue to support NTLA-2001 as a potential one-time treatment to permanently inactivate the TTR gene and reduce the disease-causing protein.

Hereditary Angioedema (HAE)

NTLA-2002: NTLA-2002 leverages Intellias proprietary in vivo LNP delivery technology to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of HAE. This investigational approach aims to prevent attacks for people living with HAE by providing continuous reduction of plasma kallikrein activity, following a single dose, and to eliminate the significant treatment burden associated with currently available HAE therapies. NTLA-2002 is being evaluated in a Phase 1/2 study in adults with Type I or Type II HAE.

Intellia is progressing the single-ascending dose portion of its first-in-human study. The Company anticipates presenting interim data in the second half of 2022, including safety, kallikrein reduction and HAE attack rate data. These initial results are expected to characterize the emerging safety and activity profile of NTLA-2002 and potentially demonstrate the modularity of Intellias proprietary CRISPR-based, LNP platform.

Alpha-1 Antitrypsin Deficiency (AATD)

NTLA-3001 for associated lung disease: NTLA-3001 is a wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to improve patient outcomes, including eliminating the need for weekly IV infusions of A1AT augmentation therapy or lung transplant in severe cases.

NTLA-2003 for associated liver disease: NTLA-2003 is a wholly owned, in vivo knockout development candidate for the treatment of AATD-associated liver disease. It is designed to inactivate the SERPINA1 gene responsible for the production of abnormal A1AT protein in the liver. This approach aims to halt the progression of liver disease and eliminate the need for liver transplant in severe cases.

Ex Vivo Program Updates

Acute Myeloid Leukemia (AML)

NTLA-5001: NTLA-5001 is an investigational autologous T cell receptor (TCR)-T cell therapy engineered to target the Wilms Tumor 1 (WT1) antigen for the treatment of all genetic subtypes of AML. In March, Intellia announced that the first patient was dosed in the Phase 1/2a first-in-human trial of NTLA-5001.

Intellia has decided to concentrate its ex vivo development efforts exclusively on allogeneic cell therapies manufactured from healthy donors. The Companys proprietary technologies, including its LNP-based cell engineering platform and novel allogeneic solution, offer significant advantages over both autologous and current investigational allogeneic approaches. Preclinical data presented on its differentiated allogeneic engineering platform showed allogeneic T cells were shielded from immune rejection, both host T and natural killer (NK) cell attack.

Intellia announced today plans to discontinue its first-in-human study of NTLA-5001, an investigational autologous TCR-T cell therapy, and is pivoting to an allogeneic version of this program currently in preclinical development. This decision is not due to any safety or efficacy data emerging from the trial. It is instead based on the potential of Intellias allogeneic platform to consistently deliver a high-quality, readily available and persistent cell product for treatment of aggressive cancers.

Preclinical data supporting the development of a WT1-directed allogeneic TCR-T cell candidate will be presented at a future scientific conference in 2022.

CD30+ Lymphomas

NTLA-6001: NTLA-6001 is a wholly owned, allogeneic CAR-T development candidate targeting CD30 for the treatment of CD30-expressing hematologic cancers, including relapsed or refractory classical Hodgkin lymphoma (cHL). NTLA-6001 is the first candidate developed using Intellias proprietary allogeneic cell engineering platform.

Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that may enable broader in vivo and ex vivo applications.

Intellia plans to advance at least one additional new in vivo development candidate by the end of 2022.

The Company plans to highlight additional advances to its proprietary technology capabilities, including both genome editing and delivery tools, at upcoming scientific conferences in 2022.

Upcoming Milestones

The Company has set forth the following for pipeline progression:

In Vivo

NTLA-2001 for ATTR amyloidosis:

NTLA-2002 for HAE: Present interim data from Phase 1/2 study in 2H 2022

NTLA-3001 for AATD: File an IND or IND-equivalent in 2023

Advance at least one additional new in vivo development candidate by the end of 2022

Ex Vivo

Modular Platform

Second Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $906.9 million as of June 30, 2022, compared to $1.1 billion as of December 31, 2021. The decrease was driven by cash used to fund operations of approximately $191.2 million as well as the acquisition of Rewrite for $45.0 million. The decrease was offset in part by $38.9 million in net equity proceeds raised from the Companys At the Market (ATM) agreement and $14.3 million in proceeds from employee-based stock plans.

Collaboration Revenue: Collaboration revenue increased by approximately $7.5 million to $14.0 million during the second quarter of 2022, compared to $6.6 million during the second quarter of 2021. The increase was primarily driven by our collaborations with AvenCell and Kyverna.

R&D Expenses: Research and development expenses increased by $31.3 million to $90.2 million during the second quarter of 2022, compared to $58.9 million during the second quarter of 2021. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs and expansion of the development organization.

G&A Expenses: General and administrative expenses increased by $5.4 million to $22.1 million during the second quarter of 2022, compared to $16.7 million during the second quarter of 2021. This increase was primarily related to employee-related expenses, including stock-based compensation of $4.5 million.

Net Loss: The Companys net loss was $100.7 million for the second quarter of 2022, compared to $68.8 million during the second quarter of 2021.

Conference Call to Discuss Second Quarter 2022 Results

The Company will discuss these results on a conference call today, Thursday, August 4, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.

Please visit this link for a simultaneous live webcast of the call.

A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellias website at intelliatx.com, beginning on August 4, at 12 p.m. ET.

About Intellia TherapeuticsIntellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. To fully realize the transformative potential of CRISPR-based technologies, Intellia is pursuing two primary approaches. The companys in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellias ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellias deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of genome editing to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on Twitter@intelliatx.

Forward-Looking Statements This press release contains forward-looking statements of Intellia Therapeutics, Inc. (Intellia or the Company) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellias beliefs and expectations concerning: its ability to successfully extend its leadership position and harness the full potential of genomic medicines to bolster its genome editing capabilities and pipeline; the safety, efficacy, success and advancement of its clinical programs for NTLA-2001 for the treatment of ATTR amyloidosis, NTLA-2002 for the treatment of hereditary angioedema (HAE) and NTLA-5001 for the treatment of acute myeloid leukemia (AML) pursuant to its clinical trial applications (CTA) and investigational new drug (IND) submissions, including the expected timing of data releases, regulatory filings, and the initiation, enrollment, and completion of clinical trials; its ability to successfully pivot to an allogeneic version of its NTLA-5001 program for the treatment of AML, including the expected timing of data releases and regulatory filings; the advancement of development candidates, such as NTLA-3001 for the treatment of alpha-1 antitrypsin deficiency (AATD)-associated lung disease, NTLA-2003 for AATD-associated liver disease and NTLA-6001 for CD30+ lymphomas, including the success of its IND-enabling studies; its ability to generate data to initiate clinical trials and the timing of CTA and IND submissions; the expansion of its CRISPR/Cas9 technology and related technologies to advance additional development candidates and timing expectations of advancing such development candidates and releasing data related to such technologies and development candidates; its ability to maintain and expand its related intellectual property portfolio; expectations of the potential impact of the coronavirus disease pandemic, including the impact of any variants, on strategy, future operations and timing of its clinical trials; and its ability to optimize the impact of its collaborations on its development programs, including, but not limited to, its collaboration with Regeneron Pharmaceuticals, Inc. and their co-development program for ATTR amyloidosis.

Any forward-looking statements in this press release are based on managements current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellias ability to protect and maintain its intellectual property position; risks related to Intellias relationship with third parties, including its contract manufacturers, licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation and conduct of studies and other development requirements for its product candidates, including uncertainties related to regulatory approvals to conduct clinical trials; risks related to the ability to develop and commercialize any one or more of Intellias product candidates successfully; risks related to the results of preclinical studies or clinical studies not being predictive of future results in connection with future studies; the risk that clinical study results will not be positive; and risks related to Intellias collaborations with Regeneron Pharmaceuticals, Inc. or its other collaborations not continuing or not being successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellias actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Intellias most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Intellias other filings with the Securities and Exchange Commission (SEC). All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.

INTELLIA THERAPEUTICS, INC.

CONSOLIDATED STATEMENTS OF OPERATIONS (UNAUDITED)

(Amounts in thousands, except per share data)

Three Months Ended June 30,

Six Months Ended June 30,

2022

2021

2022

2021

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Intellia Therapeutics Announces Second Quarter 2022 Financial Results and Highlights Recent Company Progress - Yahoo Finance

Augustine Fernandez

Medical student crime investigator Augustine Fernandezwas murdered as part of an alleged robbery in the town of Cipolletti on 5 July last, DNA of a male has been found under the left thumb of the victim.

Meanwhile, a month after the murder, the family members of the 19-year-old Pampas girl will execute tomorrow. a peaceful marchNext to the Ni Una Menos Assembly in the Plaza de la Justicia in that city of Rio Negro.

Judicial sources said experts from the Bariloche Regional Forensic Genetics Laboratory this Wednesday handed over the results of the analysis of various samples to the prosecutors office to investigate the crime, including: Traces of DNA extracted from the corpse.

According to experts, genetic material It was found in the fingernails of the index finger of the right hand and thumb of the left hand.

in bothA mixed genetic profile was obtained related to the mixing of genetic material from at least two individuals, detailed the Rio Negro Public Prosecutors Office (MPF) in an official statement.

,The genetic profile obtained from the victims sample can be mirrored in the majority, and in full, and partly, and with less amplification, of another individuals genetic profile. added the report signed by the director of the laboratory, in which he insisted that The thumb can be confirmed that the genetic profile is not that of Augustina and that of a male.

In turn, the sample was used to complete comparative expertise with the genetic profile of the victims friend, who lived in the apartment where the crime took place. leaving him as a contributor. This man had given his statement to the authorities in the initial hours of the investigation itself. Her story had already been corroborated by public and private security cameras located in different parts of the city.,

According to sources, the results of laboratory analysis are supported by various indications that are already involved in the case, and allow progress and reinforce the working hypothesis that it was a criminal cause of murder, In other words, they killed him to hide another crime, in this case, robbery.

For this reason, it remains the main line of research of MPF, although test measures continue to be produced in parallel within the framework of other hypotheses. In this context, the police of Rio Negro are continuing to search for that person. identification prepared in time by the Federal Police and, if the suspect is arrested, Forensic genetics can be compared with genetic traces obtained by a field laboratory.

In this regard, the Ministry of Security of the Provincial Arranged a reward of one million pesos for those who can provide data that helps in finding their identity or whereabouts, Any information can be provided through the prosecutors shift cell phone (0299) 154167314, emergency telephone line 911 or the nearest police unit.

As per the details available so far, The age of the man is between 20 and 30 years, his height is between 1.60 to 1.70 meters, he has fair skin and dark hair.

His most striking feature is that he has a series of tattoos on his face and hands., A tattoo on his eyebrows that can be described as the number 10 is combined with others similar to a cross. He holds a series of pictures in his hands, in which the letters that make up the word Rock stand on his fingers.

The crime took place on Saturday, July 2, at approximately 7:30 pm, in an apartment complex in Calle Confluencia at 1,300 in Cipolletti. The victim was studying medicine at the National University of Comahu (UNCO).

it is believed that Augustina was surprised by at least one criminal who entered to steal and attacked her with blows, after which she took some valuables and fled. Due to the horrors of the beating, she was transferred to the Pedro Moguilanski Hospital in Cipolletti, where she remained hospitalized until she died.

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Medical student who was beaten to death in an attack in Cipoletti: her family will donate her organs

I found him on the floor, trembling: Medical student beaten to death in Cipolletti

Heartbreaking message from the mother of the young woman who was beaten to death in Cipolletti: My child fought for the future and today we are donating his organs

Go here to read the rest:
Medical Student's Crime In Cipolletti: They Found A Man's DNA Under The Victim's Thumb - Nation World News

What weve dreamed about for several decades now is becoming reality, says Professor Ian Alexander, head of the gene therapy research unit at the Childrens Medical Research Institute. We are about to see a big rush of these therapies coming into the clinic. Its really started screaming upwards in the last few years its exponential.

We stand on the very tip of the iceberg. The first gene therapy was approved in China in 2004; over the next 10 years, global regulators approved just four more. In just the past 18 months, regulators have approved five treatments with two more awaiting final approval and another 3633 therapies in the pipeline, according to tracking by the American Society of Gene and Cell Therapy.

Were at the stage where there is a huge bulge coming down the clinical trial pipeline. Its almost exceeding capacity, says Dr Thomas Edwards, head of retinal gene therapy research at the Centre for Eye Research Australia. Its an exciting time for patients, it wasnt long ago we had nothing for them.

Many of the drugs we have, such as penicillin or Tamiflu, work by killing bacteria or viruses. Vaccination uses a dead virus to prime the immune system. Synthetic hormones like insulin treat the bodys own shortages. Chemicals in pill form, such as selective serotonin reuptake inhibitors, float through the bloodstream, enter our cells and change our chemistry.

Gene therapy is different. Rather than alter our chemistry, it treats us by changing our genotype, the way our DNA is expressed.

It is a new paradigm. It offers the first possibility of curing diseases at their root genetic cause and the possibility of a lifelong cure, says Rasko. And we are seeing that now in patients.

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Understanding Zolgensma gives you an idea of how different this new medical era will be.

Every time you go to scroll an article or turn the page in a newspaper, your brain converts that thought to a signal. It runs down your spinal cord to motor neurons, cells that reside in the cord but project thin tendrils out into the flesh. These tendrils called axons carry commands from neuron to muscle.

Like every cell in your body, each motor neuron carries a full copy of your genome, separated across 23 pairs of chromosomes and locked tight in the cells nucleus.

On chromosome five is a short stretch of genetic code known as SMN1. This gene is a blueprint for a protein crucial to the motor neurons function.

SMN1 is in an unfortunate place. The stretch of chromosome it lies in is prone to errors. Make a coding error in SMN1 and you blur the blueprint. The motor neurons struggle to build their crucial protein and soon start dying.

Without motor neurons, the signals from the brain to eat, to move, even to breathe stop getting through. In about 1 in every 10,000 babies born in Australia every year, this gene has an error.

Zolgensma, marketed by Novartis, comes in a small syringe, just 50 milliltres. Inside the syringe, in fluid, is a genetically-modified adeno-associated virus, the organic machines that make the treatment possible.

As far as science can tell, AAVs are harmless to humans. They infect us without us ever knowing. Scientists slice out the part of the viruss genetic code and replace it with a copy of SMN1. Inside the body, it crosses from the blood to the spinal cord and quickly infects motor neuron cells. Its the perfect vehicle, says Associate Professor Michelle Farrar, a paediatric neurologist who led a clinical trial of the drug at Sydney Childrens Hospitals Network.

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The virus enters the nucleus the vault where DNA is kept and releases its copy of the SMN1 gene. Unlike Gattaca-style genetic editing, the new gene is not incorporated into the patients DNA but floats nearby. Extra genetic code attached to the gene instructs the cell to activate it and start churning out copies of the key protein the motor neurons need.

Unlike most cells in the body, motor neurons dont divide; youre born with all you have. This is why losing them is so dangerous but it also means that if you can repair the faulty gene, you should have a therapy that works long-term. Some patients are now eight years post-treatment with no sign its wearing off, says Farrar.

Zolgensma does come with risks: serious liver injury or failure. Two patients on one of the drugs key clinical trials had signs of liver damage; a third had swelling on the brain requiring surgery.

Indeed, liver damage remains a problem with many gene treatments, with multiple deaths reported in clinical trials.

It remains unclear why. But the therapies rely on treating one disease by essentially infecting a patient with a benign virus, and when you put something in the blood a lot of it is going to end filtered out by the liver. One theory: in some people the immune system might spot and attack the build-up of virus in the liver, leading to extreme systemic inflammation and death.

Safety concerns have dogged gene therapy ever since the death of Jesse Gelsinger the young man who, in 1999, became the face of the treatments limitations after he died while participating in a clinical trial.

His death was a very sobering experience for the field, says Alexander from the Childrens Medical Research Institute a sign that scientists understood far less than they thought. There was a mismatch between the technology and the understanding.

Rasko is tougher on his colleagues. In 1999, when Jesse passed, essentially the whole field stunk. Everyone was accused of overhyping, and no one was delivering.

In response, the field curtailed its ambition and pivoted toward diseases that are a better match for the quickly developing technology.

Early treatments were held up because of the struggle to deliver enough of the gene without provoking a huge immune response. By switching to adeno-associated viruses small viruses that infect humans and some other primate species scientists found they could deliver more genetic code while reducing the immune response. And the field started hunting for conditions that seemed a better match for gene therapy.

Zolgensma and Spark Therapeutics Luxturna, approved for government subsidy in March, both use the same adeno-associated virus to target cells that are easy to access and do not divide.

Luxturna treats a genetic cause of blindness by supplying a replacement copy of a defective gene to cells in the retina, allowing them to make a protein crucial for sight.

The gene is small and easy to package in the virus. And the eye, you can get at it relatively easy surgically, says Eye Research Australias Edwards. And [the retina] has immune-privilege the virus does not cause a widespread immune reaction.

Both Zolgensma and Luxturna are extraordinarily expensive, raising the question of whether gene therapy will be a medicine of the rich. Experts are hopeful that wont be the case.

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Some of the early therapies will be for small groups, but eventually a gene therapy that can be used by many people will come online, says Professor Robyn Jamieson, head of the eye genetics research unit at the Childrens Medical Research Institute. Those economies of scale will push the price down for everyone.

And now the technology has been proven to work, competition among biotechs to develop new therapies is fierce. They are jaw-droppingly expensive now, says Rasko, but over time that competition should pull costs down.

And new facilities to make the viral machines at the heart of the treatment will also come online. This year NSW invested $25 million in a pilot factory to make viral vectors in Westmead.

None of this can come quickly enough for the hundreds of thousands of families across Australia living with genetic illnesses.

Shes very stubborn, very strong-willed, Adriana Baron says of her daughter, Mariana. And that helped her.Credit:Simon Schluter

To get Mariana the treatment she needed, Adriana had to battle first to get a diagnosis, then get approved for the treatment, and then get government funding to bring it into the country. But shes a fighter, just like her daughter.

Shes very stubborn, very strong-willed. And that helped her, says Adriana. If she wants to do things on her own, she tells you, I dont need any help, she does it herself.

Liam Mannixs Examine newsletter explains and analyses science with a rigorous focus on the evidence. Sign up to get it each week.

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A new era: After winding path and safety scares, gene therapy enters the clinic - Sydney Morning Herald

Researchers at the Medical College of Georgia at Augusta University have uncovered a link between disease of small blood vessels that feed the white matter of the brain and worse cognitive function in patients with Alzheimers.

White matter accounts for almost 50% of brain mass, enables different regions of the brain to communicate and is packed with microscopic arterioles that directly feed the tissue with blood, oxygen and nutrients. Changes in white matter have been linked to Alzheimers in the past. A new study is now connecting disease in the microscopic arterioles to changes in the tissue and impaired cognition.

The findings of the study, published in GeroScience revealed that the arterioles of individuals diagnosed with Alzheimers and microvascular dysfunction had difficulty dilating in comparison to individuals with Alzheimers and no microvascular dysfunction, leading to white matter injury, inflammation and cognitive decline.

The main message is the mixed pathology as we call itmicrovascular disease and Alzheimers is associated with more brain damage, more white matter damage and more inflammation, said Zsolt Bagi, PhD, professor at the Medical College of Georgia at Augusta University, and co-author of the study in a press statement.

We are proposing that if you prevent development of the microvascular component, you may at least add several years of more normal functioning to individuals with Alzheimers.

This research adds to recent findings published in European Radiology which suggest that some people with Alzheimers who have brain changes widely associated with the condition, such as amyloid plaques, may not develop dementia without this underlying vascular dysfunction.

The researchers note that vascular disease is potentially modifiable by reducing major risk factors like hypertension, obesity, diabetes and inactivity. individuals might especially benefit if they would exercise, control blood sugar level and control their blood pressure, Bagi said in a press statement.

You have some genetic predisposition but people realize that not everybody develops memory decline or cognitive deficits unless something else is coming in.

The findings add to previous research published in The Journal Of Neuroscience suggesting that small blood vessel disease may predict the severity of dementia and may help identify those patients in early enough stages of the disease which could benefit from treatments to reduce or slow vascular dysfunction, potentially delaying or reducing their cognitive loss.

The researchers agree that more studies will be needed to better understand exactly how the small blood vessel disease occurs, which could uncover potential new drug targets to intervene.

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Small Blood Vessel Disease in the Brain Linked to Worse Cognition in Alzheimer's - Inside Precision Medicine

1. Ethical Considerations in Precision Medicine and Genetic Testing in Internal Medicine Practice: A Position Paper From the American College of Physicians | Annals of Internal Medicine  Annals of Internal Medicine
2. Genetic Testing Should Be Guided by Patients' Best Interests, ACP Position Paper Says  GenomeWeb
3. ACP offers guidance on the ethical use of genetic testing and precision medicine  EurekAlert
4. The Ethical Responsibilities of Precision Medicine According to ACP  MD Magazine
5. View Full Coverage on Google News

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Ethical Considerations in Precision Medicine and Genetic Testing in Internal Medicine Practice: A Position Paper From the American College of...

CARLSBAD, Calif., July 26, 2022 /PRNewswire/ -- Ionis Pharmaceuticals (Nasdaq: IONS) today announced that the U.S. Food and Drug Administration (FDA) has accepted a New Drug Application (NDA) for tofersen, an investigational antisense medicine for the treatment of superoxide dismutase 1 amyotrophic lateral sclerosis (SOD1-ALS). The NDA was submitted by Biogen, which licensed tofersen from Ionis in 2018. The application has been granted priority review and given a Prescription Drug User Fee Act action date of Jan. 25, 2023. The FDA has noted that it is currently planning to hold an Advisory Committee meeting for this application. The average life expectancy for people with ALS is three to five years from time of symptom onset; patients with some SOD1 mutations have an even shorter life expectancy. There is currently no treatment targeted for SOD1-ALS.

"Acceptance of the new drug application for tofersen is a monumental milestone, not just for Ionis but for all people with SOD1-ALS, their families and healthcare professionals battling this devastating disease. To them we extend our deepest gratitude. Their courage has been instrumental to the achievement of this goal," said C. Frank Bennett, Ph.D., executive vice president, chief scientific officer and franchise leader for neurological programs at Ionis. "We also want to thank Biogen for their commitment to advancing tofersen, which, if approved, will be the first treatment that targets a genetic cause of ALS." Dr. Bennett added, "Acceptance of the NDA for tofersen further strengthens Ionis' platform strategy to target all forms of ALS and central nervous system disorders more broadly."

Biogen is seeking approval of tofersen under the FDA's accelerated approval pathway, based on the use of neurofilament as a surrogate biomarker that is reasonably likely to predict clinical benefit. Neurofilaments are normal proteins found in healthy neurons, that are increased in blood and cerebrospinal fluid when damage has been done to neurons or their axons and are a marker of neurodegeneration. In ALS, higher levels of neurofilaments have been found to predict more rapid decline in clinical function and shortened survival. Tofersen study results suggest reductions in neurofilament preceded and predicted slowing of decline in measures of clinical and respiratory function, strength and quality of life. Biogen has stated its commitment to ongoing data generation and finalizing the confirmatory package with the FDA.

The tofersen NDA included results from a Phase 1 study in healthy volunteers, a Phase 1/2 study evaluating ascending dose levels, the Phase 3 VALOR study, and the open label extension (OLE) study. Also included are the most current 12-month integrated results from VALOR and the OLE study, recently presented at the European Network to Cure ALS (ENCALS) annual meeting.

As reported in October 2021, VALOR, a six-month Phase 3 randomized study, did not meet the primary endpoint of change from baseline to week 28 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale. However, trends of reduced disease progression across multiple secondary and exploratory endpoints were observed. The 12-month VALOR and OLE integrated data showed that earlier initiation of tofersen led to sustained reductions in neurofilament, a marker of neurodegeneration, and slowed decline across multiple efficacy endpoints.

In the 12-month data, the most common adverse events (AEs) in participants receiving tofersen in VALOR and the OLE study were headache, procedural pain, fall, back pain and pain in extremities. Most AEs in both VALOR and the OLE were mild to moderate in severity. Serious AEs were reported in 36.5 percent of participants who received tofersen in VALOR and/or the OLE and 17.3 percent of participants discontinued treatment due to an AE.

During the FDA review period Biogen will maintain its early access program for tofersen, now with participants in over a dozen countries. The open-label extension and Phase 3 ATLAS study in presymptomatic individuals with a SOD1 genetic mutation remain ongoing. Biogen is actively engaging with other regulators around the world and will provide updates when appropriate.

About Tofersen

Tofersen is an antisense medicine being evaluated for the potential treatment of SOD1-ALS. Tofersen binds to SOD1 mRNA, allowing for its degradation by RNase-H in an effort to reduce synthesis of SOD1 protein production. In addition to the ongoing open label extension of VALOR, tofersen is being studied in the Phase 3 ATLAS study designed to evaluate whether tofersen can delay clinical onset when initiated in presymptomatic individuals with a SOD1 genetic mutation and biomarker evidence of disease activity. Biogen licensed tofersen from Ionis under a collaborative development and license agreement.

About Amyotrophic Lateral Sclerosis and SOD1-ALS

Amyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and the spinal cord that are responsible for controlling voluntary muscle movement. People with ALS experience muscle weakness and atrophy, causing them to lose independence as they steadily lose the ability to move, speak, eat, and eventually breathe. Average life expectancy for people with ALS is three to five years from time of symptom onset. Patients with some SOD1 mutations have an even shorter life expectancy.

Multiple genes have been implicated in ALS. Genetic testing helps determine if a person's ALS is associated with a genetic mutation, even in individuals without a family history of the disease. Currently, there are no genetically targeted treatment options for ALS. Mutations in the SOD1 gene are responsible for approximately 2 percent of the estimated 168,000 people who have ALS globally (SOD1-ALS).

AboutIonis Pharmaceuticals, Inc.

For more than 30 years, Ionis has been the leader in RNA-targeted therapy, pioneering new markets and changing standards of care with its novel antisense technology. Ionis currently has three marketed medicines and a premier late-stage pipeline highlighted by industry-leading cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision of becoming a leading, fully integrated biotechnology company.

To learn more about Ionis visit http://www.ionispharma.com and follow us on Twitter @ionispharma.

Ionis' Forward-looking Statements

This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of Ionis' technologies, tofersen and other products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to, those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements.

Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended Dec. 31, 2021, and the most recent Form 10-Q quarterly filing, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers toIonis Pharmaceuticalsand its subsidiaries.

Ionis Pharmaceuticals is a trademark ofIonis Pharmaceuticals, Inc.

SOURCE Ionis Pharmaceuticals, Inc.

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Ionis announces that FDA accepts New Drug Application and grants Priority Review of tofersen for a rare, genetic form of ALS - PR Newswire