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Monday, March 11, 2024

Moderna recent events

 Recently, on clinicaltrials.govMerck & Co Inc 

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 posted a new trial of Moderna Inc’s 
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 V940, an individualized neoantigen therapy (INT), plus pembrolizumab for locally resectable advanced cutaneous squamous cell carcinoma (LA cSCC). 

Phase 2 has three arms V940 plus pembrolizumab given as neoadjuvant and adjuvant treatment with standard of care (SOC), standard of care (surgical resection with/without adjuvant radiation therapy (RT) only at investigator’s discretion) and pembrolizumab monotherapy given as neoadjuvant and adjuvant treatment with SOC. 

This phase will assess the safety and efficacy of V940 in combination with pembrolizumab as neoadjuvant and adjuvant therapy in participants with resectable LA cSCC compared to standard-of-care SOC only. 

The primary hypothesis is that V940 plus pembrolizumab with SOC is superior to SOC only concerning event-free survival (EFS) as assessed by the investigator. 

Phase 3 expansion will be determined by a prespecified Go-No-Go decision in which 412 additional participants will be randomized to V940 plus pembrolizumab with SOC and SOC only, without changing the inclusion/exclusion criteria for the additional enrollment or study endpoints.

The study is not yet enrolling participants. It is expected to start next month, and the study is expected to conclude by 2029, as per the government website.

The companies are already collaborating for two Phase 3 trials of V940 (mRNA-4157) plus Keytruda for melanoma and non-small cell lung cancer.

Jefferies, in its note, writes that this third new trial suggests even more investment put to work on the program and speaks to continued confidence in a broad program. The analyst notes that cSCC is ~20% of malignant cutaneous melanoma and a more aggressive form of skin cancer.

RBC Capital says this is the first potentially pivotal trial that will also explore both neo-and adjuvant therapy, and cSCC is on the rise, with around one million cases diagnosed in the U.S. each year.

https://www.benzinga.com/analyst-ratings/analyst-color/24/03/37595998/whats-going-on-with-moderna-stock-on-monday

Indivior Publishes on Nasal Spray Rapid Reversal of Opioid-Induced Respiratory Depression

 

  • This head-to-head pharmacodynamic study in healthy volunteers examined the ability of both OPVEE and intranasal naloxone to reverse opioid-induced respiratory depression, which is the shallow and slow breathing associated with an opioid overdose
  • In this model, OPVEE 2.7mg reversed respiratory depression to 95% of pre-opioid baseline within 5 minutes; a similar reversal following a 4 mg dose of intranasal naloxone required 20 minutes
  • "Reversal of opioid-induced respiratory depression in healthy volunteers: comparison of intranasal nalmefene and intranasal naloxone", was published in the Journal of Clinical Pharmacology (Reversal of Opioid‐Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone - Ellison - The Journal of Clinical Pharmacology - Wiley Online Library) and is the first head-to-head comparison examining the effects of 2.7 mg intranasal (IN) nalmefene (OPVEE) and 4 mg IN naloxone on opioid-induced respiratory depression. This study was a part of the OPVEE development program and reviewed by the FDA as part of the approval process.

Implantable Brain-Computer Interface Collaborative Community to Drive Innovation in Neurotech

 Mass General Brigham is establishing the Implantable Brain-Computer Interface Collaborative Community (iBCI-CC). This is the first Collaborative Community in the clinical neurosciences that has participation from the U.S. Food and Drug Administration (FDA).

BCIs are devices that interface with the nervous system and use software to interpret neural activity. Commonly, they are designed for improved access to communication or other technologies for people with physical disability. Implantable BCIs are investigational devices that hold the promise of unlocking new frontiers in restorative neurotechnology, offering potential breakthroughs in neurorehabilitation and in restoring function for people living with neurologic disease or injury.

The iBCI-CC (https://www.ibci-cc.org/) is a groundbreaking initiative aimed at fostering collaboration among diverse stakeholders to accelerate the development, safety and accessibility of iBCI technologies. The iBCI-CC brings together researchers, clinicians, medical device manufacturers, patient advocacy groups and individuals with lived experience of neurological conditions. This collaborative effort aims to propel the field of iBCIs forward by employing harmonized approaches that drive continuous innovation and ensure equitable access to these transformative technologies.

One of the first milestones for the iBCI-CC was to engage the participation of the FDA. “Brain-computer interfaces have the potential to restore lost function for patients suffering from a variety of neurological conditions. However, there are clinical, regulatory, coverage and payment questions that remain, which may impede patient access to this novel technology,” said David McMullen, M.D., Director of the Office of Neurological and Physical Medicine Devices in the FDA’s Center for Devices and Radiological Health (CDRH), and FDA member of the iBCI-CC. “The IBCI-CC will serve as an open venue to identify, discuss and develop approaches for overcoming these hurdles.”

The iBCI-CC will hold regular meetings open both to its members and the public to ensure inclusivity and transparency. Mass General Brigham will serve as the convener of the iBCI-CC, providing administrative support and ensuring alignment with the community’s objectives.

Over the past year, the iBCI-CC was organized by the interdisciplinary collaboration of leaders including Leigh Hochberg, MD, PhD, an internationally respected leader in BCI development and clinical testing and director of the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital; Jennifer French, MBA, executive director of the Neurotech Network and a Paralympic silver medalist; and Joe Lennerz, MD, PhD, a regulatory science expert and director of the Pathology Innovation Collaborative Community. These three organizers lead a distinguished group of Charter Signatories representing a diverse range of expertise and organizations.

“As a neurointensive care physician, I know how many patients with neurologic disorders could benefit from these devices,” said Dr. Hochberg. “Increasing discoveries in academia and the launch of multiple iBCI and related neurotech companies means that the time is right to identify common goals and metrics so that iBCIs are not only safe and effective, but also have thoroughly considered the design and function preferences of the people who hope to use them.”

Jennifer French said, “Bringing diverse perspectives together, including those with lived experience, is a critical component to help address complex issues facing this field.” French has decades of experience working in the neurotech and patient advocacy fields. Living with a spinal cord injury, she also uses an implanted neurotech device for daily functions. “This ecosystem of neuroscience is on the cusp to collectively move the field forward by addressing access to the latest groundbreaking technology, in an equitable and ethical way. We can’t wait to engage and recruit the broader BCI community.”

Joe Lennerz, MD, PhD, emphasized, “Engaging in pre-competitive initiatives offers an often-overlooked avenue to drive meaningful progress. The collaboration of numerous thought leaders plays a pivotal role, with a crucial emphasis on regulatory engagement to unlock benefits for patients.”

The iBCI-CC is supported by key stakeholders within the Mass General Brigham system. Merit Cudkowicz, MD, MSc, chair of the Neurology Department, director of the Sean M. Healey and AMG Center for ALS at Massachusetts General Hospital, and Julianne Dorn Professor of Neurology at Harvard Medical School, said, “There is tremendous excitement in the ALS [amyotrophic lateral sclerosis, or Lou Gehrig’s disease] community for new devices that could ease and improve the ability of people with advanced ALS to communicate with their family, friends, and care partners. This important collaborative community will help to speed the development of a new class of neurologic devices to help our patients.”

Professor Thomas Oxley, CEO & Founder of Synchron, stated, “It’s an honor to be part of this community, at such a pivotal moment, driving innovation in this nascent field of neuroprosthetics to potentially help so many people. It’s through a diverse group like this that we can engineer solutions with a patient-first ethos.”

Bailey McGuire, program manager of strategy and operations at Mass General Brigham’s Data Science Office, said, “We are thrilled to convene the iBCI-CC at Mass General Brigham’s DSO. By providing an administrative infrastructure, we want to help the iBCI-CC advance regulatory science and accelerate the availability of iBCI solutions that incorporate novel hardware and software that can benefit individuals with neurological conditions. We’re excited to help in this incredible space.

For more information about the iBCI-CC, please visit https://www.ibci-cc.org/.

About Mass General Brigham 
Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

About the iBCI-CC Organizers 
Leigh Hochberg, MD, PhD is a neurointensivist at Massachusetts General Hospital’s Department of Neurology, where he directs the MGH Center for Neurotechnology and Neurorecovery. He is also the IDE Sponsor-Investigator and Director of the BrainGate clinical trials, conducted by a consortium of scientists and clinicians at Brown, Emory, MGH, VA Providence, Stanford, and UC-Davis; the L. Herbert Ballou University Professor of Engineering and Professor of Brain Science at Brown University; Senior Lecturer on Neurology at Harvard Medical School; and Director, VA RR&D Center for Neurorestoration and Neurotechnology in Providence.

Jennifer French, MBA, is the Executive Director of Neurotech Network, a nonprofit organization that focuses on education and advocacy of neurotechnologies. She serves on several Boards including the IEEE Neuroethics InitiativeInstitute of NeuroethicsOpenMind platform, BRAIN Initiative Multi-Council and Neuroethics Working Groups, and the American Brain Coalition. She is the author of On My Feet Again (Neurotech Press, 2013) and is co-author of Bionic Pioneers (Neurotech Press, 2014). French lives with tetraplegia due to a spinal cord injury. She is an early user of an experimental implanted neural prosthesis for paralysis and is the Past-President and Founding member of the North American SCI Consortium.

Joe Lennerz, MD PhD, serves as the Chief Scientific Officer at BostonGene, an AI analytics and genomics startup based in Boston. Dr. Lennerz obtained a PhD in neurosciences, specializing in electrophysiology. He works on biomarker development and migraine research. Additionally, he is the co-founder and leader of the Pathology Innovation Collaborative Community, a regulatory science initiative focusing on diagnostics and software as a medical device (SaMD), convened by the Medical Device Innovation Consortium. He also serves as the co-chair of the federal Clinical Laboratory Fee Schedule (CLFS) advisory panel to the Centers for Medicare & Medicaid Services (CMS).

https://www.biospace.com/article/releases/implantable-brain-computer-interface-collaborative-community-ibci-cc-to-drive-innovation-in-neurotechnology/

Boehringer, Sosei Ink Potential $732M Deal for Schizophrenia Treatment

 German pharma Boehringer Ingelheim is paying €25 million ($27.3 million) upfront and further milestone payments of up to €670 million ($732.6 million) in a deal with Sosei Heptares to develop potential first-in-class treatments targeting all symptoms of schizophrenia, the companies announced Monday.

Under the agreement, Boehringer Ingelheim has the exclusive option to license Sosei Heptares’ portfolio of GPR52 agonists, which are a G protein-coupled receptor target. Sosei is also eligible for an option payment of €60 million ($65.5 million) and possible development, regulatory and commercialization milestone payments. The London-based pharma, whose parent company is Japan’s Sosei Group Corporation, will also net customary tiered royalties on future product sales.

The drug class is intended to treat the positive, negative, and cognitive symptoms of schizophrenia at the same time. Positive symptoms include hallucinations and delusions, while negative symptoms are apathy and withdrawal. Cognitive symptoms include attention, planning and memory deficits.

Boehringer will have the exclusive option to license the portfolio of GPR 52 agonists after the completion of Sosei’s Phase I and Phase Ib trials and Phase II enabling activities with the antipsychotic HTL0048149. Sosei will retain control and sponsor the trials until the potential option is exercised, which is estimated to occur in 2025. The portfolio that Boehringer gains will include the HTL’149 asset and other “differentiated backup compounds” that are designed by Sosei.  

“This collaboration highlights the potential GPR52 has shown in preclinical research as a novel, first-in-class target for treating schizophrenia and related neurological disorders. We’re delighted to partner with Boehringer Ingelheim and leverage its leading expertise in neurological disease research and innovation,” Matt Barnes, president of Heptares Therapeutics and head of UK R&D at Sosei Heptares, said in a statement, “Together, we will focus on accelerating the development of this highly innovative program, which is currently in a Phase 1 clinical study, towards patients in need.”

Hugh Marston, global head CNS discovery research at Boehringer Ingelheim, said in a statement that the partnership with Sosei “is highly complementary to our other development programs aiming to bring a new precision medicine approach to the treatment of mental health disorders with therapies, which we hope will transform the lives of those living with schizophrenia.”

Boehringer has been securing several deals over the past few months. In early January 2024, the company announced it entered into a multi-target collaboration agreement with Suzhou Robi Life Science and Ribocure Pharmaceuticals to develop an siRNA treatment for nonalcoholic or metabolic dysfunction-associated steatohepatitis in a deal potentially worth over $2 billion.

In November 2023, Boehringer inked a potential $509 million collaboration agreement with Phenomic AI to develop targets for stroma-rich cancers, some of the hardest cancers to treat, utilizing its single-cell RNA computing platform. 

https://www.biospace.com/article/boehringer-sosei-ink-potential-732m-deal-for-schizophrenia-treatment-/

Doctors, Dictators, And The Medical Autocracy

  by Amy Denney via The Epoch Times (emphasis ours),

Jean Wendrick acknowledges that she’s been mostly unhealthy her whole life—suffering from diabetes since she was in her 20s and overcoming breast cancer more recently.

At a doctor’s appointment last year, Ms. Wendrick learned she has osteopenia, a condition in which her body isn’t making new bone cells quickly enough, which often leads to osteoporosis. Her doctor suggested medication—the same type her mother has been taking.

It was devastating to me,” she said. “My mom is hunched over with osteoporosis and can only look at the floor. She’s in so much pain, and she took all the meds. It was all for nothing.

While Ms. Wendrick can see her potential future when looking at her 86-year-old mother, she also finds reasons, when thinking of her 18-year-old daughter, Victoria, whom she had at age 47, to make the changes that can restore her health.

Thus, Ms. Wendrick became determined six months ago that she would live out her years in the best possible health. She knew it would demand real change and a true return to a healthy lifestyle—something her doctor’s prescriptions could never give her.

The Doctor’s Dilemma

Ms. Wendrick’s experience is common. Facing devastating illness, patients are offered drugs that have little effect and create problems that patients may never be told about.

While some doctors will do little beyond suggesting surgery or a new prescription, many others do recommend their patients make lifestyle changes to fundamentally resolve the cause of chronic conditions.

However, all too often, these recommendations come as brief commands to “lose weight,” “exercise more,” or “eat better” and are often served with a sprinkle of judgment.

Health care providers may then blame patients for their inability to follow such orders.

A study in Finland echoes findings in other settings where physicians and nurses say patients with obesity, Type 2 diabetes, high blood pressure, and who smoke, just won’t do what they are told.

“A majority [of both physicians and nurses] agreed that a major barrier to the treatment of lifestyle-related conditions is patients’ unwillingness to change their habits,” the study states.

And all too often this is true. However, research also suggests doctors and nurses dispense such advice in ineffective ways. Giving orders in brief and hurried appointments is not an effective way to get patients to address long-standing habits, like eating certain foods, advised Dr. Ann Lindsay, a physician and clinical professor in medicine at Stanford, in an article in Stanford Medicine’s Scope magazine.

Everybody basically wants to lead a healthy life,” Dr. Lindsay told Scope, “but there are different beliefs and obstacles that contribute to ambivalence.

Helping patients overcome those beliefs and navigate those obstacles simply isn’t in the job description for many health care practitioners.

One part of the issue is a lack of time. Another part of the issue is that physicians simply don’t know how to help patients or communicate these issues well. Many doctors have no meaningful relationship with the people whose lives depend on them.

Physicians who learn how to communicate well are more than twice as effective in getting patients to make lifestyle changes, said Dr. Lindsay.

One of the reasons for the rise of functional medicine is a desire from both patients and physicians to focus on the systemic lifestyle factors behind disease.

A Different Approach to Medicine

Making changes requires patients to take responsibility—and health care practitioners to effectively support that change, say experts.

“Before I had excuses. I ate what I wanted when I wanted, and I was eating for emotions. I always had symptoms. I didn’t do any exercise. It was awful,” Ms. Wendrick recalled. “Now, there is a reason for me to get up in the morning and finally take care of me. I know it takes discipline and determination to get results.”

Ms. Wendrick is on a mission to get her diabetes under control, lose weight, and strengthen her bones. She hired a new doctor to help her succeed, Dr. Scott Doughty, a family doctor at U.P. Holistic Medicine in Michigan. Ms. Wendrick calls him “the boss.” She’s lost 30 pounds so far and said she feels like she’s in her 20s.

For the first time in her health care experience, Ms. Wendrick felt listened to and that she had suitable options and a support system that would allow her to avoid the poor prognosis she was facing. It became easier for her to comply because she felt in control and supported by Dr. Doughty, she said.

Ms. Wendrick isn’t an exception. Patient engagement, motivation, and support are vital ingredients for healing disease from the standpoint of functional medicine and research studies.

The American Medical Association (AMA) says doctors need to help patients find their motivation and give them small but meaningful targets for improvement—like a 5 percent weight reduction.

The AMA also raises the need for an engaging coach, someone capable of getting patients to participate in lifestyle programs.

Unfortunately, these programs are still hard to come by in many areas and physicians may not even be aware they exist. All too often, doctors simply tell patients they need to take a new drug or have surgery, with little in the way of discussion.

Medicinal Commands

2019 study revealed that a shared power balance between patients and health care providers was critical to active patient participation and adherence to treatment in chronic illnesses.

Patients cannot be forced to follow a lifestyle dictated by others,” notes the study published in the International Journal of Community Based Nursing and Midwifery. “The finding suggests that adherence is facilitated by empowerment that includes competence in self-care, adaptability, and persistence in treatment.

Telling people they need to “stop this or stop that” almost universally fails, Dr. Joel Evans, founder and director of the Center for Functional Medicine, told The Epoch Times. It’s more effective, he said, to find beneficial things to add to behavior such as eating more fruits and vegetables.

“By talking to patients this way, they feel more cared for, and they’re more likely to participate in the creation of a plan ... and they’re more likely to follow the plan,” Dr. Evans said. “The doctor dictator doesn’t work.”

While it can be frustrating to encounter doctors who don’t offer options or support, patients can voice concerns, ask for more resources, or find help elsewhere as Ms. Wendrick did.

Doctors As Dictators

Physicians find themselves in an impossible bind. They often believe they must convey a sense of certainty and authority to give their patients confidence in prescribed treatments—and yet there is little certainty in medicine. This can lead to issuing orders rather than engaging patients in more meaningful conversations.

Read more here...

https://www.zerohedge.com/medical/doctors-dictators-and-medical-autocracy

Deluge Of Violent Crime Sees Philly Transit Boss Call For National Guard, Following NYC's Lead

 Transit Workers Union Local 234 President Brian Pollitt is demanding accountability from Gov. Josh Shapiro, Mayor Cherelle Parker, and SEPTA officials after a string of violent crimes on and around Philadelphia mass transit over the last few weeks. 

In fact, he says he has been calling for National Guard deployment on SEPTA - similar to how New York City has deployed the National Guard on MTA - for four years, according to WKYW.

“I think that governor needs a round of applause because they're going through the very same thing that we're going through,” Pollitt said of New York City. 

He says many drivers are seeking retirement because of how dangerous the job has gotten and that it is tough recruiting new drivers. “And I got young people coming in the door and once they come in here and see how things are, they're going out there looking for other opportunities,” he said. 

Recall last Thursday we wrote about 8 teens who were shot near a SEPTA bus in Northeast Philadelphia. The incident came just hours after the last shooting injuring four and killing one involving mass transit in Philadelphia.

The incident occurred at around 3 p.m. near Northeast High School at Cottman and Rising Sun avenues, where students were waiting for a bus. Three assailants opened fire, shooting over 30 rounds from across the street, wounding eight teenagers.

Surveillance captured them exiting a blue Hyundai Sonata and attacking as a bus arrived, then fleeing. The victims, aged between 15 and 17, included seven boys and a girl; two are critically injured.

Descriptions of the gunmen have been released. The shooting prompted a lockdown at a nearby elementary school and hit two SEPTA buses without injuring passengers.

Police have impounded a car believed to be involved in the shooting, seizing a blue Hyundai Sonata found parked on Roselyn Street in the Olney area of the city on Wednesday night. The vehicle, now at a local impound lot, is said to match the description of the dark blue 2019 Hyundai Sonata identified as the getaway car in surveillance footage.

Mayor Cherelle Parker commented last week: "The purpose of our being here today is to inform you all that enough is enough. That every law enforcement partner that we have here in the city of Philadelphia is actively engaged in working together to ensure that every resource that is needed is readily available so that the work can be done to solve crimes."

https://www.zerohedge.com/markets/deluge-violent-crime-sees-septa-union-boss-call-national-guard-philly-mass-transit