Can cell therapy treat muscular dystrophy? German billionaire's anti-aging startup aims to find out

 Gene therapy companies have faced huge hurdles trying to deliver healthy genes into muscular dystrophy patients’ muscle cells, so here’s an idea: Why don’t we just replace the muscle cells themselves?

Over the last two years, Vita Therapeutics has been exploring that possibility, building on early stem cell work from Johns Hopkins professors Gabsang Lee and Kathryn Wagner. And on Tuesday they announced a $32 million Series A to begin to move their first therapy into the clinic, where they hope it will help rebuild muscle in patients with a type of dystrophy that afflicts the arms and legs.

The startup is the second portfolio company unveiled by Cambrian Biopharma, the anti-aging portfolio company launched last year by ATAI co-founder Christian Angermayer. (The first was the now public cancer startup, Sensei Bio). Cambrian is taking the approach ATAI took to psychedelic therapies, bringing a broad range of related companies under a single roof, and applying it anti-aging therapies, said CEO and co-founder James Peyer.

They’ve invested in several technologies that could slow or reverse the effects of aging, such as boosting mitochondria or regenerating tissue. But they’re applying them first in diseases where they could have a more immediate impact.

For muscular dystrophies, Vita will try to take the same strategy that CRISPR Therapeutics and other gene editing companies have used for genetic blood disorders such as sickle cell disease. This is not a simple task: Doctors have decades of experience removing and replacing a patient’s blood cells — and over a decade of experience engineering those cells — but it’s not as if you can just extract all of a patient’s muscle cells and then put them back.

Accordingly, companies such as AskBio and Sarepta devised ways of correcting muscle cells in vivo, strapping healthy genes onto (mostly) harmless viruses and administering them to patients as gene therapy. That process, though, has faced a number of hurdles: The genes involved don’t fit well onto the viruses used for gene therapy and the viruses don’t reach all the muscle. Early clinical trials yielded mixed results.

Peyer said Vita doesn’t need to replace all a patient’s muscle cells. Instead, they’ll take cells from a patient’s blood, turn them into stem cells in the lab, use CRISPR to correct the disease-causing mutations and finally manipulate them into a class of cells called myosatellite cells. These cells are responsible for producing mature muscle cells.

Vita, led by first time CEO Doug Falk and Hopkins professor Peter Anderson as CSO, believes that they can inject these cells into different parts of the body, where they will produce healthy muscle cells that can replace the damaged ones.

“We have this amazing data in mice that they reintegrate into the muscles,” Peyer told Endpoints News. “And in the mice can improve time on a treadmill or grip strength… It’s really awesome functional outcomes.”

Vita will look to start a clinical trial next year for limb girdle dystrophy, where they will compete with a gene therapy from Sarepta. But even if the therapy works, Peyer acknowledged there will be steep limitations.

For one, it’s not clear how long the cells will last. And although the approach might work to replenish muscle cells in the limbs, there are no myosatellite cells in the heart. For many patients with muscular dystrophy, including those with Duchenne, it’s degeneration in these vital muscles that ultimately brings the worst symptoms and death.

“Yeah,” Peyer said, “That’s why we’re not starting immediately DMD.”

https://endpts.com/can-a-cell-therapy-treat-muscular-dystrophy-a-german-billionaires-anti-aging-startup-is-trying-to-find-out/

ICER revises its view of Aduhelm’s price – but not by much

 The Institute for Clinical and Economic Review (ICER) was very damning of Biogen’s new Alzheimer’s disease therapy Aduhelm when it issued its first report on the drug last month, and a swift update to its deliberations won’t be much comfort to the company.

The cost-effectiveness watchdog has revised its calculation of a fair price range for Aduhelm (aducanumab) upwards, but only by a small amount.

Biogen would still have to cut the $56,000 list price for a year’s treatment with the drug by 85% to 95% to reach ICER’s new $3,000 to $8,400 range, up marginally from the $2,500 to $8,300 range set in its earlier draft analysis.

The only reason for the change is that the FDA-approved labelling for the drug requires fewer MRI scans per patient than were carried out during clinical trials of the anti-amyloid antibody.

That’s small comfort for Biogen, given that US lawmakers have launched an investigation into Aduhelm’s price as well as the sequence of events that led to the drug’s approval despite questions about its clinical benefit.

The Kaiser Family Foundation recently estimated that of prescribed at full price, Medicare could spend $57 billion or more per year on Aduhelm – more than Medicare Part B outpatient cover spends on all other drugs combined.

Discussing the latest update, ICER’s chief medical officer David Rind acknowledged that the first effective therapy with Alzheimer’s will warrant “a very high price in the US health system,” but the non-profit group is adamant that Aduhelm does not fit the bill.

“After months of delving into the data, and working with patient groups, clinical experts, and the manufacturer to gain their perspectives, our judgment remains that the evidence on aducanumab is insufficient to be able to demonstrate that patients get benefits that would outweigh the risks and harms of this treatment,” he said.

Biogen’s price would only be in the acceptable range of $50,000 to $70,000 per year for a hypothetical therapy that – when given as a maintenance therapy – could completely halt the progression of dementia in people with Alzheimer’s.

ICER’s assessment has been challenged by a number of groups including the Alzheimer’s Association which challenges its decision to “blend” data from the two phase 3 trials submitted in support of Aduhelm’s approval, and for overplaying the side effects of the antibody which it says are “manageable”.

It isn’t defending Biogen’s price though, describing it earlier this month as “unacceptable” and for many patient “an insurmountable barrier to access”.

Biogen – and other amyloid drug developers Eli Lilly and Genentech – also took issue with ICER’s methodology, including the way it has calculated cost per quality adjusted life year (QALY) figures – a widely used measure of cost-effectiveness used by health technology assessment (HTA) agencies.

They also said the analysis failed to take into account the wider burden of Alzheimer’s on society as a whole.

Biogen will have an opportunity to defend its pricing of Aduhelm at an ICER-sponsored meeting scheduled for 15 July that will hear representation from the company, neurologists, patients, the Alzheimer’s association, payer organisations and former FDA Commissioner Mark McLellan.

https://pharmaphorum.com/news/icer-revises-its-view-of-aduhelms-price-but-not-by-much/

Merck partners neuroloop on bioelectronic device for inflammation

 Merck KGaA has joined forces with a unit of medtech firm B Braun – neuroloop – on a way to treat inflammatory diseases using neurostimulator devices.

The German drugmaker will work with startup neuroloop on bioelectronics, put simply the harnessing of electrical stimulation to treat human disease, with a focus on chronic conditions like arthritis and inflammatory bowel disease.

neuroloop – a spinout of Freiburg University in Germany formed in 2016 – has been working to date on using its device as an implant to lower blood pressure, among other applications. The Merck collaboration will concentrate on using the device alongside anti-inflammatory drug therapies.

Merck chief executive Belén Garijo said that these kind of neurostimulator approaches “show great promise in helping to improve therapeutic outcomes and efficiency for patients with chronic inflammatory diseases.”

The tie-up with neuroloop and B Braun will bring together their expertise in this area with Merck’s knowhow in “electronics, medicines and drug delivery,” he added.

The German startup has developed a cuff electrode that allows selective stimulation of fibres in the vagus nerve, which carries an extensive range of signals from the body to the brain and vice versa.

One hypothetical neural circuit – known as the ‘inflammatory reflex’ – is thought to ferry sensory information about inflammation to the brain as well as anti-inflammatory signals back to the cells in tissues.

An open-label, proof-of-concept study looking at a vagus nerve-stimulating implant as a therapy for rheumatoid arthritis was published in 2016, showing that the device was able to reduce the production of inflammatory cytokines in the body and finding some evidence of reduced disease severity.

The approach sounds simple in principle, but neuroloop chief executive Michael Lauk cautioned that “identifying the specific disease relevant nerve signal patterns and subsequently modulating these signals via stimulation are major challenges in the field of bioelectronics.”

“Together with the strong preclinical and clinical expertise of Merck and our platform which enables multi-channel selective stimulation, we are well positioned to potentially solve these crucial challenges and offer neurostimulator treatment to patients suffering from chronic inflammatory diseases,” he added.

Merck and its partners are hoping to have initial data from trials of the bioelectronic device by the end of 2022 , which will then be used to establish a clinical development plan with an eye on getting approvals in major markets like Europe and the US.

The drugmaker – which has made bioelectronics a key research area along with other pharma companies like GlaxoSmithKline – says novel bioelectronic devices also have the potential to monitor disease conditions.

https://pharmaphorum.com/news/merck-partners-neuroloop-on-bioelectronic-device-for-inflammation/

Medicaid expansion didn't lead to changes in hospitalizations in safety-net facilities: Study

 The Affordable Care Act’s Medicaid expansion did not lead to patients migrating from safety-net hospitals to other facilities, underpinning a major goal of the initiative, a new study found.

The study conducted by Boston Medical Center and published in the Journal of the American Medical Association Wednesday comes as the Biden administration has made improving access to care and erasing racial and ethnic minority coverage gaps a major priority.

“While we thought that the expansion of Medicaid might lead some racial/ethnic minority patients to transfer their care to non-safety-net hospitals, where specialty care services might often be more accessible, our study results demonstrate that was not the case,” said Karen Lasser, the lead study author, in a statement.

Researchers looked at discharge data from 11 states that expanded Medicaid under ACA and six that did not. All the states had 18.2 million Medicaid and uninsured patient discharges, with nearly 60% from states with expanded Medicaid and 40.6% in non-expansion states, a release on the study said.

The study found no significant changes in safety-net hospitalizations among Medicaid or uninsured patients in states that did and did not expand Medicaid. There were also no major changes among racial and ethnic minority groups or among low-income patients.

“It is possible that patients are satisfied with the care they receive and benefit from services that may be unavailable in other settings, such as assistance with insurance, interpretation and case management,” the study said.

But another theory is that the “persistence of structural racism and residential segregation prevents patients from transferring care to non-[safety-net hospitals],” the study said. “Extending health insurance coverage alone appears insufficient to reduce hospital segregations by race/ethnicity or socioeconomic status.”

The study could inform the Biden administration’s efforts to close racial and ethnic disparities in healthcare. The Department of Health and Human Services is exploring new requirements including hospitals to produce race and ethnicity data as part of payment models.

The White House is also making moves to get 12 holdout states to sign up for Medicaid expansion. The American Rescue Plan Act raised the federal matching rate by 5% for Medicaid payments for newly expanded states.

https://www.fiercehealthcare.com/hospitals/study-medicaid-expansion-didn-t-lead-to-changes-hospitalizations-safety-net-facilities

Stephens starts HealthEquity at Overweight, target $100

 

• Stephens initiated coverage of HealthEquity (HQY) with an Overweight rating and $100 price target. The firm believes as the largest health savings account custodian, HealthEquity is well positioned to benefit from industry growth trends as higher-deductible health plans are becoming more of the norm. The firm sees near and longer-term catalysts that should drive above-peer top and bottom line growth.

https://www.briefing.com/search?Ticker=TREND

Biotech week ahead, July 6

 Biotech stocks advanced for a second week in running, with stocks reacting to pending releases for the second quarter and the first-half of the year.

The week witnessed a few COVID-19 disappointments. CureVac N.V. CVAC 4.55% confirmed the sub-par efficacy data for its first-generation vaccine against the novel coronavirus.

Altimmune, Inc. ALT 6.97% shares fell about 43% for the week after it announced it is rolling up its intranasal COVID-19 vaccine program. The company was also forced to stop enrollment into the phase 1/2 trial for T-COVID, its single dose intranasal therapeutic for treating early COVID-19. Angion Biomedica Corp. ANGN 7.02% decided to shelve its COVID-19 program following a failed Phase 2 study.

Several R&D collaborations and licensing deals were announced during the week. Alector, Inc. 

ALEC 57.12% shares jumped Friday after it announced an out-licensing deal with GlaxoSmithKline plc GSK 0.62% for two monoclonal antibodies being evaluated for the treatment of neurodegenerative diseases.

Among the stocks that made their Wall Street debuts were Acumen Pharmaceuticals, Inc. ABOS 0.9%, medical device maker CVRx, Inc. CVRX 2.34% and Aerovate Therapeutics, Inc. (AVTE), a cardiopulmonary diseases focused biopharma. POINT Biopharma Inc. PNT 11.54% made its debut through a SPAC deal.

Here are the key catalytic events for the unfolding week.

Conferences

• European Crohn's and Colitis Organization, or ECCO, 16th Annual Congress: July 2-3 & July 8-10
• Society for Reproductive Investigation, SRI, 68th Annual Meeting: July 6-9
• European Academy of Allergy and Clinical Immunology, or EAACI, Annual Congress 2021, to be held virtually: July 10-16

PDUFA Dates

The FDA is scheduled to rule on ChemoCentryx, Inc.'s CCXI 0.15% new drug application for avacopan, an orally-administered small molecule being evaluated for the treatment of ANCA-associated vasculitis and other complement-driven autoimmune and inflammatory diseases. An FDA panel that reviewed the NDA in early May issued a split verdict.

Clinical Readouts/Presentations

ObsEva SA OBSV 1.34% is due to present at the SRI annual meeting results from the proof-of-concept trial of ebopiprant for the treatment of spontaneous preterm labor. The oral presentation is scheduled for Wednesday, July 7, at 4-5:30 pm

Morphic Holding, Inc. MORF 1.01% will host a webcast and conference call at 8 am on Friday, July 9 to discuss results from the phase 1 study of MORF-057 in inflammatory bowel disease. The company will also present the data at the ECCO Congress.

Pharvaris N.V. PHVS 6.48% will present clinical data for oral PHA121 that is being evaluated for the treatment of hereditary angioedema, as an e-Poster at the EAACI annual congress. The abstract will be published on the EAACI website on Saturday, July 10. The virtual poster presentation will be on the EAACI website from July 10-16.

IPOs    

IPO Quiet Period Expiry

Janux Therapeutics, Inc. JANX 0.24%
Alzamend Neuro, Inc. ALZN 5.21%   
https://www.benzinga.com/general/biotech/21/07/21832024/the-week-ahead-in-biotech-focus-on-chemocentryx-fda-decision-conference-presentations-in-a-light-

Epsilon variant mutations contribute to COVID immune evasion

 Three mutations in the Epsilon coronavirus Spike protein dampen the neutralizing potency of antibodies induced by current vaccines or past COVID infections.

The mutations give this coronavirus variant of concern a means to totally evade specific monoclonal antibodies used in clinics and reduces the effectiveness of antibodies from the plasma of vaccinated people.

To better understand the exact immune escape strategies at work here, the scientists visualized this variant’s infection machinery to see what is different from the original configuration of the pandemic coronavirus, and what the implications of these changes are.

The international project was led by David Veesler’s lab in the Department of Biochemistry at the University of Washington in Seattle and by Luca Piccoli and Davide Corti of Vir Biotechnology.

For several years, the Veesler lab and its collaborators have been exploring the molecular conformation and infection mechanics of SARS-like coronaviruses. They also examine how antibodies attempt to block infection mechanisms, and how variants come up with new dodges.

Their latest data shows that the Epsilon variant “relies on an indirect and unusual neutralization-escape strategy,” according to the researchers.

Their findings are published as a First Release paper in the latest edition of Science. Read the paper.

A molecular clock analysis timed the emergence of the precursor to the Epsilon variant to May of 2020 in California. By summer of 2020 it had diverged into its B.1.427/B.1.429 lineages. COVID cases from the variant increased quickly, and the variant soon became widespread in the United States.  It has now been reported in at least 34 other countries.

To learn more about the characteristics of the Epsilon variant, the researchers tested the resilience against the Epsilon variant of plasma from people who were exposed the virus, as well as vaccinated people.  The neutralizing potency of the plasma against the Epsilon variant of concern was reduced about 2 to 3.5 fold.

Like the original SARS-CoV-2, the variant infects target cells through its spike glycoprotein – the structure that crowns the surface of the virus.  The researchers found that the Epsilon mutations were responsible for rearrangements in critical areas of the spike glycoprotein; electron cryomicroscopy studies showed structural changes in these areas. Visualizing these mutations help explain why antibodies had difficulty binding to the spike glycoprotein.

One of the three mutations in the Epsilon variant affected the receptor binding domain on the spike glycoprotein. This mutation reduced the neutralizing activity of 14 out of 34 neutralizing antibodies specific to that domain, including clinical stage antibodies.

The other two of the three mutations in the variant affected the N-terminal domain on the spike glycoprotein. The researchers used mass spectrometry and structural analysis to find that a part of the coronavirus N-terminal domain was remodeled by these mutations. The signal peptide cleavage site was shifted in the NTD antigenic supersite, and a new disulphide bond was formed.  This resulted in a total loss of neutralization by 10 out of 10 antibodies tested specific to the N-terminal domain in the spike glycoprotein.

The scientist believed that uncovering mechanisms of immune evasion, such as this newfound mechanism based on signal peptide modification, is as important as variant surveillance through RNA sequencing. Together, they note, such efforts could help to successfully counter the ongoing pandemic.

The lead scientists on this project were Matthew McCallum and Alexandra C. Walls of the UW School of Medicine Department of Biochemistry; Jessica Bassi and Anna de Marco of Humabs Biomed; and Alex Chen of Vir Biotechnology.

This study was supported by the National Institute of Allergy and Infectious Diseases (DP1AI158186 and HHSN272201700059C, U01 AI151698-01), Pew Biomedical Scholars Award, Investigators in the Pathogenesis of Infectious Disease Awards from the Burroughs Wellcome Fund, Fast Grants, Natural Sciences and Engineering Research Council of Canada, and Pasteur Institute.

https://newsroom.uw.edu/news/epsilon-variant-mutations-contribute-covid-immune-evasion