Most vaccines, from measles to Covid-19, require a series of multiple shots before the recipient is considered fully vaccinated. To make that easier to achieve, MIT researchers have developed microparticles that can be tuned to deliver their payload at different time points, which could be used to create “self-boosting” vaccines.
In a new study, the researchers describe how these particles degrade over time, and how they can be tuned to release their contents at different time points. The study also offers insights into how the contents can be protected from losing their stability as they wait to be released.
Using these particles, which resemble tiny coffee cups sealed with a lid, researchers could design vaccines that would need to be given just once, and would then “self-boost” at a specified point in the future. The particles can remain under the skin until the vaccine is released and then break down, just like resorbable sutures.
This type of vaccine delivery could be particularly useful for administering childhood vaccinations in regions where people don’t have frequent access to medical care, the researchers say.
“This is a platform that can be broadly applicable to all types of vaccines, including recombinant protein-based vaccines, DNA-based vaccines, even RNA-based vaccines,” says Ana Jaklenec, a research scientist at MIT’s Koch Institute for Integrative Cancer Research. “Understanding the process of how the vaccines are released, which is what we described in this paper, has allowed us to work on formulations that address some of the instability that could be induced over time.”
This approach could also be used to deliver a range of other therapeutics, including cancer drugs, hormone therapy, and biologic drugs, the researchers say.
Jaklenec and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, are the senior authors of the new study, which appears today in Science Advances. Morteza Sarmadi, a research specialist at the Koch Institute and recent MIT PhD recipient, is the lead author of the paper.
Staggered Drug Release
The researchers first described their new microfabrication technique for making these hollow microparticles in a 2017 Science paper. The particles are made from PLGA, a biocompatible polymer that has already been approved for use in medical devices such as implants, sutures, and prosthetic devices.
To create cup-shaped particles, the researchers create arrays of silicon molds that are used to shape the PLGA cups and lids. Once the array of polymer cups has been formed, the researchers employed a custom-built, automated dispensing system to fill each cup with a drug or vaccine. After the cups are filled, the lids are aligned and lowered onto each cup, and the system is heated slightly until the cup and lid fuse together, sealing the drug inside.
This technique, called SEAL (StampEd Assembly of polymer Layers), can be used to produce particles of any shape or size. In a paper recently published in the journal Small Methods, lead author Ilin Sadeghi, an MIT postdoc, and others created a new version of the technique that allows for simplified and larger-scale manufacturing of the particles.
In the new Science Advances study, the researchers wanted to learn more about how the particles degrade over time, what causes the particles to release their contents, and whether it might be possible to enhance the stability of the drugs or vaccines carried within the particles.
“We wanted to understand mechanistically what’s happening, and how that information can be used to help stabilize drugs and vaccines and optimize their kinetics,” Jaklenec says.
Their studies of the release mechanism revealed that the PLGA polymers that make up the particles are gradually cleaved by water, and when enough of these polymers have broken down, the lid becomes very porous. Very soon after these pores appear, the lid breaks apart, spilling out the contents.
“We realized that sudden pore formation prior to the release time point is the key that leads to this pulsatile release,” Sarmadi says. “We see no pores for a long period of time, and then all of a sudden we see a significant increase in the porosity of the system.”
The researchers then set out to analyze how a variety of design parameters, include the size and shape of the particles and the composition of the polymers used to make them, affect the timing of drug release.
To their surprise, the researchers found that particle size and shape had little effect on drug release kinetics. This sets the particles apart from most other types of drug delivery particles, whose size plays a significant role in the timing of drug release. Instead, the PLGA particles release their payload at different times based on differences in the composition of the polymer and the chemical groups attached the ends of the polymers.
“If you want the particle to release after six months for a certain application, we use the corresponding polymer, or if we want it to release after two days, we use another polymer,” Sarmadi says. “A broad range of applications can benefit from this observation.”
Stabilizing the Payload
The researchers also investigated how changes in environmental pH affect the particles. When water breaks down the PLGA polymers, the byproducts include lactic acid and glycolic acid, which make the overall environment more acidic. This can damage the drugs carried within the particles, which are usually proteins or nucleic acids that are sensitive to pH.
In an ongoing study, the researchers are now working on ways to counteract this increase in acidity, which they hope will improve the stability of the payload carried within the particles.
To help with future particle design, the researchers also developed a computational model that can take many different design parameters into account and predict how a particular particle will degrade in the body. This type of model could be used to guide the development of the type of PLGA particles that the researchers focused on in this study, or other types of microfabricated or 3D-printed particles or medical devices.
The research team has already used this strategy to design a self-boosting polio vaccine, which is now being tested in animals. Usually, the polio vaccine has to be given as a series of two to four separate injections.
“We believe these core shell particles have the potential to create a safe, single-injection, self-boosting vaccine in which a cocktail of particles with different release times can be created by changing the composition. Such a single injection approach has the potential to not only improve patient compliance but also increase cellular and humoral immune responses to the vaccine,” Langer says.
This type of drug delivery could also be useful for treating diseases such as cancer. In a 2020 Science Translational Medicine study, the researchers published a paper in which they showed that they could deliver drugs that stimulate the STING pathway, which promotes immune responses in the environment surrounding a tumor, in several mouse models of cancer. After being injected into tumors, the particles delivered several doses of the drug over several months, which inhibited tumor growth and reduced metastasis in the treated animals.
Continued progress for programs targeting eye diseases with the submission of an IND application for OCU200
Expanded portfolio now includes inhaled vaccines for COVID-19, seasonal flu, and a combination COVID-19+seasonal flu vaccine
MALVERN, Pa., Feb. 28, 2023 (GLOBE NEWSWIRE) — Ocugen, Inc. (Ocugen or the Company) (NASDAQ: OCGN), a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines, today reported fourth quarter and full year 2022 financial results along with a general business update.
“We continue to grow and advance as a diversified biotechnology organization as reflected in our accomplishments of 2022,” said Dr. Shankar Musunuri, Chairman, Chief Executive Officer, and Co-Founder of Ocugen. “Our pipeline has been expanded to appropriately address the current challenges and gaps in the fight against COVID-19, application of OCU410 to address Stargardt (a rare eye disease), and our novel approach to address dry age-related macular degeneration (dAMD)—a disease affecting vision in over 266 million people worldwide.
“Following FDA concurrence in the fourth quarter of 2022 on a confirmatory Phase 3 clinical trial design for NeoCart®, we are developing internal capabilities to move our regenerative medicine asset, NeoCart®, into the clinic next year.”
“The FDA has granted expanded orphan drug designations to OCU400 for the treatment of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA),” said Dr. Musunuri. “These broad, gene-agnostic designations are encouraging at this stage in the development of OCU400.”
“During our first decade, we have built a strong foundation for addressing the diseases and conditions we aim to treat. We delivered on our promise to file an OCU200 IND in the first quarter of 2023 and look forward to delivering on important milestones in 2023, especially regarding preliminary efficacy data for gene therapy product OCU400, as we progress toward realizing our long-term vision to address unmet medical needs through courageous innovation,” Dr. Musunuri concluded.
Business Updates
Ophthalmic Gene Therapies
OCU400 – Established the high dose as the maximum tolerable dose, completed retinitis pigmentosa patient enrollment, and continuing to enroll patients with LCA to receive the high dose. Ocugen intends to initiate a Phase 3 clinical trial near the end of 2023.
OCU410 and OCU410ST – Executing IND-enabling studies and intend to submit IND applications in the second quarter of 2023 to initiate Phase 1/2 clinical trials in dry AMD (geographic atrophy) and Stargardt disease.
Ophthalmic Biologic Product
OCU200 – Submitted an IND application on February 27, 2023 to initiate a Phase 1 clinical trial targeting diabetic macular edema.
Regenerative Cell Therapies
NeoCart® – Received concurrence from the FDA on the confirmatory Phase 3 clinical trial design. Ocugen intends to initiate the Phase 3 clinical trial in the first half of 2024. Ocugen is renovating its facility to accommodate cGMP manufacturing of NeoCart® for clinical trials and beyond.
Vaccines Portfolio
OCU500 Series – Developing a novel mucosal vaccine platform which includes OCU500, a bivalent COVID-19 inhaled vaccine; OCU510, a seasonal quadrivalent flu inhaled vaccine; and OCU520 a combination quadrivalent seasonal flu and bivalent COVID-19 inhaled vaccine.
COVAXIN™ (BBV152) – Completed enrollment in Phase 2/3 immuno-bridging and broadening clinical trial in fourth quarter 2022.
Financial Results
Fourth quarter — Research and development expenses for the three months ended December 31, 2022, were $17.2 million compared to $7.1 million for the three months ended December 31, 2021. General and administrative expenses for the three months ended December 31, 2022, were $6.9 million compared to $7.5 million for the three months ended December 31, 2021. Ocugen reported a $0.10 net loss per common share for the three months ended December 31, 2022, compared to a $0.07 net loss per common share for the three months ended December 31, 2021.
Full year — Research and development expenses for the year ended December 31, 2022, were $49.8 million compared to $35.1 million for the year ended December 31, 2021. General and administrative expenses for the year ended December 31, 2022, were $35.1 million compared to $22.9 million for the year ended December 31, 2021. Ocugen reported a $0.38 net loss per common share for the year ended December 31, 2022, compared to a $0.30 net loss per common share for the year ended December 31, 2021.
Ocugen’s cash, cash equivalents, restricted cash, and investments totaled $90.9 million as of December 31, 2022, compared to $95.1 million as of December 31, 2021. The Company estimates that its current cash, cash equivalents, and investments will enable it to fund its operations into the first quarter of 2024. The Company had 221.6 million shares of common stock outstanding as of December 31, 2022.
Conference Call and Webcast Details
Ocugen has scheduled a conference call and webcast for 8:30 a.m. ET today to discuss the financial results and recent business highlights. Ocugen’s senior management team will host the call, which will be open to all listeners. There will also be a question-and-answer session following the prepared remarks.
Attendees are invited to participate on the call or webcast using the following details:
Dial-in Numbers: (800) 715-9871 for U.S. callers and (646) 307-1963 for international callers Conference ID: 8912239 Webcast: Available on Ocugen’s investor site
A replay of the call and archived webcast will be available for approximately 45 days following the event on the Ocugen investor site.
About Ocugen, Inc. Ocugen, Inc. is a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines that improve health and offer hope for patients across the globe. We are making an impact on patient’s lives through courageous innovation—forging new scientific paths that harness our unique intellectual and human capital. Our breakthrough modifier gene therapy platform has the potential to treat multiple retinal diseases with a single product, and we are advancing research in infectious diseases to support public health and orthopedic diseases to address unmet medical needs.
Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, which are subject to risks and uncertainties. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks, and uncertainties that may cause actual events or results to differ materially from our current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission (SEC), including the risk factors described in the section entitled “Risk Factors” in the quarterly and annual reports that we file with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. Except as required by law, we assume no obligation to update forward-looking statements contained in this press release whether as a result of new information, future events, or otherwise, after the date of this press release.
Contact: Tiffany Hamilton Head of Communications IR@ocugen.com
PDS Biotech is a clinical-stage immunotherapy company developing a growing pipeline of molecularly targeted cancer and infectious disease immunotherapies based on the Company’s proprietary Versamune® and Infectimune™ T-cell activating technology platforms. Our Versamune®-based products have demonstrated the potential to overcome the limitations of current immunotherapy by inducing in vivo, large quantities of high-quality, highly potent polyfunctional tumor specific CD4+ helper and CD8+ killer T-cells. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. The Company’s pipeline products address various cancers including HPV16-associated cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung, prostate and ovarian cancers.
Robert LeBoyer, Vice President, Research Analyst, Life Sciences , Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
Triple Therapy Advances. PDS Biotech announced that the FDA has agreed to requirements for a registration trial using PDS0101 “Triple Combination” therapy in head and neck cancer. The study will test the combination of PDS0101, PDS0301, and a commercially available checkpoint inhibitor. We believe the changes from the previous trial should make regulatory approval faster, with additional tumor types added after market entry.
New Combination Eliminates An Unapproved Checkpoint Inhibitor. The new Triple Combination uses PDS010 to stimulate an immune response against the HPV antigen, PDS0301 to stimulate a robust immune response, and a checkpoint inhibitor to allow the immune system to recognize the tumor cells. The previous trial included bintrafusp alfa, an experimental checkpoint inhibitor. We believe the change to an approved checkpoint inhibitor simplifies the regulatory path.
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This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
MALVERN, Pa., Feb. 27, 2023 (GLOBE NEWSWIRE) — Ocugen, Inc. (“Ocugen” or the “Company”) (NASDAQ: OCGN), a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines, today announced that it has submitted an Investigational New Drug application (IND) with the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial of OCU200, a fusion protein with a distinct mechanism of action (MOA), for the treatment of diabetic macular edema (DME). This regulatory milestone fulfills the Company’s commitment to file the IND for OCU200 within the first quarter of 2023.
“Today’s achievement is an important step towards fulfilling our mission to bring novel therapeutics to address limitations of the current standard of care or unmet medical needs in hard-to-treat blindness diseases,” said Dr. Arun Upadhyay, Chief Scientific Officer at Ocugen. “We are encouraged by the potential for OCU200 to provide a new treatment option for the significant percentage of people living with DME, including non-responders to the current standard of care.”
The planned Phase 1 clinical study will assess the unilateral intravitreal administration of OCU200 alone or in combination with an approved anti-VEGF therapy in participants with DME. This is a multicenter, open-label, dose-ranging study with 3 cohorts in the dose-escalation portion of the study and 1 cohort in the combination therapy portion of the study.
DME is one of the most common vision-threatening diseases occurring in people with diabetes and includes blurriness in vision and progressive vision loss as the disease progresses. Approximately 745,000 people in the United States are affected with DME, and this number is expected to further increase as the number of people with diabetes increases.
The Company intends to pursue additional indications for OCU200 to potentially treat diabetic retinopathy and wet age-related macular degeneration, which combined affect nearly 9.0 million Americans.
About Ocugen, Inc. Ocugen, Inc. is a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologics, and vaccines, that improve health and offer hope for patients across the globe. We are making an impact on patient’s lives through courageous innovation—forging new scientific paths that harness our unique intellectual and human capital. Our breakthrough modifier gene therapy platform has the potential to treat multiple retinal diseases with a single product, and we are advancing research in infectious diseases to support public health and orthopedic diseases to address unmet medical needs. Discover more at www.ocugen.com and follow us on Twitter and LinkedIn.
About OCU200 OCU200 is a novel fusion protein consisting of human transferrin linked to human tumstatin. It exerts anti-proliferative, anti-inflammatory, and anti-oxidative effects by selective targeting to the retinal and choroidal tissues. OCU200 potentially showcases better bioavailability and tissue penetrance than tumstatin alone due to transferrin and provides distinct MOA binding through αVβ3 integrin pathways that can potentially reduce the number of injections for patients.
OCU200 can potentially be used for the treatment of diabetic macular edema, diabetic retinopathy, and wet age-related macular degeneration. These diseases, combined, account for approximately 10 million cases in the U.S.
Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, which are subject to risks and uncertainties. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks, and uncertainties that may cause actual events or results to differ materially from our current expectations. These and other risks and uncertainties are more fully described in our periodic filings with the Securities and Exchange Commission (SEC), including the risk factors described in the section entitled “Risk Factors” in the quarterly and annual reports that we file with the SEC. Any forward-looking statements that we make in this press release speak only as of the date of this press release. Except as required by law, we assume no obligation to update forward-looking statements contained in this press release whether as a result of new information, future events, or otherwise, after the date of this press release.
Contact: Tiffany Hamilton Head of Communications IR@ocugen.com
Received guidance on registrational path for combination in recurrent/metastatic, immune checkpoint inhibitor refractory head and neck cancer
FLORHAM PARK, N.J., Feb. 27, 2023 (GLOBE NEWSWIRE) — PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of targeted immunotherapies for cancer and infectious disease, announced the successful completion of a Type B meeting with the U.S. Food and Drug Administration (FDA) for a combination therapy of PDS0101, PDS0301 and an FDA-approved immune checkpoint inhibitor (ICI) for the treatment of recurrent/metastatic human papilloma virus (HPV)-positive, ICI refractory head and neck cancer. Head and neck cancers are the most common of all HPV-positive cancers and the number of cases is growing rapidly, according to the National Cancer Institute (NCI), one of the National Institutes of Health (NIH). There remains a critical unmet medical need to develop new treatment options for patients who have failed treatment with ICIs.
In recent interactions with the FDA, PDS Biotech has confirmed the required contents of the study design for a potential registrational trial of the combination of PDS0101, PDS0301 and a commercial immune checkpoint inhibitor. PDS0101, PDS Biotech’s lead candidate, is a Versamune® based investigational immunotherapy designed to stimulate a potent targeted T cell attack against HPV16-positive cancers. PDS0301 is a novel, proprietary investigational tumor-targeting fusion protein of Interleukin 12 (IL-12) that enhances the proliferation, potency and longevity of T cells in the tumor microenvironment, and is designed to overcome tumor immune suppression utilizing a different mechanism from checkpoint inhibitors. The combination of Versamune® and IL-12 is patented by PDS Biotech. In a National Cancer Institute (NCI)-led clinical trial in advanced HPV-positive ICI refractory patients, the combination of PDS0101 and PDS0301 administered with an investigational bi-functional ICI resulted in a median overall survival of 21 months, which compares favorably to the historical median survival of 3-4 months.
“We are pleased with the guidance from the FDA on key elements of a study design to progress the development of our assets, PDS0101 and PDS0301, in combination with a commercial immune checkpoint inhibitor,” said Dr. Frank Bedu-Addo, Chief Executive Officer of PDS Biotech. “This concurrence to substitute an FDA-approved commercially available ICI for the investigational agent studied in the NCI trial simplifies the regulatory pathway for this triple combination.”
Dr. Bedu-Addo continued, “Versamune® based investigational immunotherapies in combination with PDS0301 represent a potentially transformative treatment approach for recurrent/metastatic, ICI refractory cancer patients with poor survival prognosis. We remain committed to addressing unmet needs in cancer with more effective immunotherapy.”
About PDS0101 PDS0101, PDS Biotech’s lead candidate, is a novel investigational human papilloma virus (HPV)-targeted immunotherapy that stimulates a potent targeted T cell attack against HPV-positive cancers. PDS
Baudax Bio is a pharmaceutical company focused on innovative products for acute care settings. ANJESO is the first and only 24-hour, intravenous (IV) COX-2 preferential non-steroidal anti-inflammatory (NSAID) for the management of moderate to severe pain. In addition to ANJESO, Baudax Bio has a pipeline of other innovative pharmaceutical assets including two novel neuromuscular blocking agents (NMBs) and a proprietary chemical reversal agent specific to these NMBs. For more information, please visit www.baudaxbio.com.
Gregory Aurand, Senior Research Analyst, Healthcare Services & Medical Devices, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
Baudax Bio reported 4Q 2022. While we had removed 4Q ANJESO revenues with the announced ANJESO discontinuation at the end of December, the Company reported 4Q revenues of $0.310 million in the quarter. Net loss per share for 4Q 2022 was $12.33 per share as compared to our outlook of $9.76 per share loss as the Company took additional write-offs related to ANJESO.
Baudax Bio reported full year 2022. For the year 2022, Baudax Bio generated revenues of $1.27 million, up from $1.08 million in the 2021 year. The Company took a write-down for impairment of intangibles of $19.7 million. The full year impairment write-down for property and equipment totaled $4.2 million. The reported full year 2022 net loss was $58.8 million or a loss of $177.30 per share compared to our full year 2022 expected loss of $55.3 million or $189.44 per share.
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This Company Sponsored Research is provided by Noble Capital Markets, Inc., a FINRA and S.E.C. registered broker-dealer (B/D).
*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
Use of Psychedelics to Treat PTSD, OCD, Depression and Chronic Pain – a Researcher Discusses Recent Trials, Possible Risks
New research is exploring whether psychedelic drugs, taken under strict medical supervision, might help in treating post-traumatic stress disorder, chronic pain, depression and obsessive-compulsive disorder. Dr. Jennifer Mitchell – a professor in the Departments of Neurology and Psychiatry & Behavioral Science in the School of Medicine at the University of California, San Francisco was interviewed by SciLine. She discusses what scientists have found to date about the effectiveness of these drugs in treating these disorders and how best for them to be administered. Highlights and key excerpts of the interview have been transcribed and published below.
What are psychedelic drugs and how do they work?
Dr. Jennifer Mitchell: Psychedelic basically means “mind manifesting,” suggesting that the compound assists one in uncovering subject matter that perhaps is otherwise deeply hidden from the conscious mind.
It’s a slightly different term from hallucinogen, which you see used almost interchangeably at times with the term psychedelic.
A hallucinogen by definition is something that makes you see, hear, smell something that isn’t otherwise there, so you can imagine there’s a lot of overlap between psychedelics and hallucinogens.
Which types of psychedelic drugs are being studied by researchers for potential therapeutic use?
Dr. Jennifer Mitchell: The two most well studied drugs at this point are MDMA and psilocybin.
MDMA is being evaluated mainly for treatment of post-traumatic stress disorder treatments, and psilocybin mainly for treatment of resistant depression and major depressive disorder.
MDMA is the furthest along because there’s phase 3 data (data from late-stage research) and the possibility that a new drug application would be submitted to the FDA sometime later this year.
LSD is also being evaluated for a number of different indications, most notably obsessive-compulsive disorder.
And then a couple of sort of heavier hitters are now being tested in primarily healthy control populations, including drugs like mescaline and ayahuasca.
What have scientists discovered about whether these drugs are effective in treating health problems like PTSD or chronic pain?
Dr. Jennifer Mitchell: The drugs so far appear to be quite effective. I think one key, though, is that they’re typically being administered in conjunction with some form of psychotherapy.
So it’s important to keep that in mind when we look at the results from some of these recent trials that these are not drugs that are being administered in isolation. You are not taking home a bottle of pills and taking those twice a day as you would, say, an antidepressant. These are administered in a very particular way.
What is involved in therapeutic treatment using these drugs?
Dr. Jennifer Mitchell: Typically, prior to taking the drug at all, subjects participate in a number of preparatory sessions so that they understand a little bit about what is going to happen on an experimental session day.
And then subjects come into a room that looks very much like a comfortable living room, and they spend all day there. The drug is administered typically in the morning. For psilocybin, you’re looking at a six-hour dosing session, and for MDMA, an eight-hour dosing session.
You are in the company of a group of trained providers: therapists, psychedelic facilitators, psychiatrists and clinical research coordinators.
What are the potential risks of using psychedelic drugs for therapeutic purposes?
Dr. Jennifer Mitchell: One concern we’ve had is cardiovascular risk, and so we are taking great care in some of the clinical trials at present to evaluate cardiovascular burden, including heart attack risk, during and after the experiment. This evaluation includes tracking the heart rate and blood pressure of the participants.
In addition, researchers are worried about suicidality, in part because these are treatment-resistant populations that we’re starting off with, and so there’s a concern that perhaps, if they’re destabilized – either by the psychedelic, or just by tapering off their other meds in order to be part of a psychedelic trial – that we could run the risk of suicidality.
Lastly, I think the FDA has been concerned about the possibility that psychedelics are addictive, and so we’ve been following up with study participants to ensure that they aren’t engaging in drug seeking or drug taking outside of the study.
What do we know about the safety of taking psychedelics outside the clinical context?
Dr. Jennifer Mitchell: I think we’ve all heard stories from the ‘60s and ’70s of people taking psychedelics and having very bad experiences. What we know now is that the environment in which you take the psychedelic is of the utmost importance. It’s not appropriate at this point to try to take some of these substances or replicate some of these protocols on your own without oversight.
Watch the full interview to hear more about psychedelic medicine.
SciLine is a free service based at the nonprofit American Association for the Advancement of Science that helps journalists include scientific evidence and experts in their news stories.
Company Focuses on Development of Neuromuscular Blocking Agents
Phase II Randomized Trial for BX1000 Initiated, Positive Interim Results Announced; Completion of Study Enrollment Expected Q1 2023, Top Line Results Expected Early Q2 2023
BX2000 Dose Escalation Study Progressing
$5 Million in Financing Secured through Public Offering
MALVERN, Pa., Feb. 23, 2023 (GLOBE NEWSWIRE) — Baudax Bio, Inc. (Nasdaq:BXRX) (the “Company”), a pharmaceutical company focused on innovative products for hospital and related settings, today reported financial results for the fourth quarter and year ended December 31, 2022, updated the status of the neuromuscular blocking (NMB) agent development program, and provided an overview of other corporate and financial developments.
“During our fourth quarter we refocused our priorities on our NMB portfolio, initiating our Phase II trial for BX1000 and advancing our Phase I dose escalation trial for BX2000,” said Gerri Henwood, Baudax Bio’s President and Chief Executive Officer. “The encouraging interim data we announced from the BX1000 trial showed all patients treated to date have met the criteria for Good or Excellent intubating conditions at 60 seconds, and that BX1000 has been generally well tolerated. We believe these data speak to the potential of our NMB portfolio to improve patient management and deliver cost efficiencies in procedures where NMB is required. We expect to complete enrollment in the BX1000 trial during the first quarter of 2023, and to announce top line data early in the second quarter of 2023. Concurrently, BX2000, our ultrashort acting NMB, is continuing through its dose escalation study, which we expect to complete by the end of 2023. BX3000, our NMB reversal agent, remains on track, and we expect to complete the nonclinical and manufacturing studies needed to support an IND filing for BX3000, the NMB reversal agent in the summer of 2023. Data from these trials will provide us with insight on the profiles of the two blocking agents, which will contribute to decisions to move forward later in 2023.”
“Due to persistent economic challenges facing hospitals, as previously disclosed, we have taken the strategic decision to discontinue commercialization of ANJESO,” continued Ms. Henwood. “We continue to believe in ANJESO’s advantages over other non-opioid pain therapies, as well as its potential to overcome many of the issues associated with commonly prescribed opioid therapeutics.”
Fourth Quarter 2022 and Recent Business Highlights
NMBs
BX1000 (IV Intermediate duration of action). Results for a planned interim analysis of the Phase II trial for BX1000 were announced in January 2023. This randomized, double-blind, active-controlled clinical trial comparing three different doses of BX1000 to a standard dose of rocuronium (rocuronium bromide 0.6 mg/kg IV Bolus) is planned to enroll a total of 80 adult patients undergoing elective surgery utilizing total intravenous anesthesia currently at a single clinical site in the U.S. The primary efficacy endpoint is the proportion of patients meeting criteria for Good or Excellent intubating conditions using a standardized scale. Additionally, the trial is evaluating the safety and tolerability profile of BX1000 and rocuronium in this patient population.
BX1000 Interim Data. The pre-planned interim analysis evaluated the intubating conditions for each randomized patient after administration of study drug in a blinded fashion. In the 20-patient cohort, 5 patients per group received one of the study medications. All 20 patients were observed to have met the criteria for Good or Excellent intubating conditions at 60 seconds. Nineteen of the subjects were successfully intubated following the assessment at 60 seconds, with one remaining subject successfully intubated following the assessment at 90 seconds. Study treatments were generally well tolerated with no occurrence of severe or serious adverse events. This blinded interim analysis did not result in the decision to drop any of the four study groups nor any decision to adjust planned study enrollment numbers.
BX2000 (IV Ultra-short duration of action). Cohort enrollment is ongoing for the Phase I dose escalation study evaluating the safety, tolerability, and pharmacokinetics of BX2000 in intubated healthy volunteers. This study is comprised of likely seven or eight dosing cohorts and each cohort is planned to enroll eight patients. The first and second cohorts have been dosed and enrollment of the third cohort is underway. The Company expects to complete enrollment of the remaining cohorts in the study by the end of 2023.
BX3000 (Reversal agent). Baudax Bio expects to complete nonclinical studies and manufacturing data required to support the IND for BX3000 in the summer of 2023. Early single agent clinical trials of BX3000 will not require intubation and so would be expected to progress quickly once the IND is active, and trials are ready to initiate. The Company believes progress towards a reversal study using BX3000 in patients who have received BX1000 could begin before the end of 2023.
The Company believes the data from the ongoing clinical trials for BX1000 and BX2000 will contribute to decisions to move forward later in 2023.
ANJESO
ANJESO U.S. Commercialization Discontinued. Despite having distinct benefits as the first and only once-daily, non-opioid IV analgesic, market conditions are not favorable for the introduction and commercialization of a new pain management product in the hospital market. As a result, Baudax Bio has formally discontinued the commercialization of ANJESO and the product is currently on hold due to these business conditions.
Corporate and Financial
Closed $5 million public offering – on December 6, 2022 the Company closed a public offering of an aggregate of 1,042,787 shares of its common stock (or pre-funded warrants in lieu thereof), Series A-3 warrants to purchase up to 1,042,787 shares of common stock and Series A-4 warrants to purchase 1,042,787 shares of common stock, at a combined public offering price of $4.795 per share (or pre-funded warrant) and accompanying warrants. The Series A-3 warrants have an exercise price of $4.50 per share, are exercisable immediately upon issuance and expire five years from the date of issuance, and the Series A-4 warrants have an exercise price of $4.50 per share, are exercisable immediately and expire thirteen months from the date of issuance. The Company intends to use the net proceeds from this offering for working capital, pipeline development activities and general corporate purposes. In January 2023, 961,787 warrants were exercised providing $4.3 million in cash to the Company.
Financial Results for the Three Months Ended December 31, 2022
As of December 31, 2022, Baudax had cash and cash equivalents of $5.3 million.
Net product revenue related to sales of ANJESO in the U.S., recognized according to U.S. GAAP, for the three months ended December 31, 2022 was $0.3 million. This compares to $0.4 million for the three months ended December 31, 2021, a decrease of $0.1 million, resulting from the impact of the reduction in our field staff in 2022 and the impact of our discontinuation of commercialization in the fourth quarter of 2022. While utilizing the title model of distribution, product revenue was recognized as shipments were made to the Company’s third-party logistics provider.
Cost of sales for the three months ended December 31, 2022 was $4.8 million, compared to $0.6 million for the three months ended December 31, 2021, an increase of $4.2 million, and consisted of product costs, royalty expense and certain fixed costs associated with the manufacturing of ANJESO, including supply chain and quality costs. The increase of $4.2 million was primarily a result of an increase in the non-cash charge for inventory reserve expense of $4.4 million, partially offset by the decrease in fixed personnel related costs of $0.2 million. Certain product costs of ANJESO units recognized as revenue during the three months ended December 31, 2022 and 2021 were expensed prior to the FDA approval of ANJESO in February 2020, and therefore are not included in cost of sales during the related periods.
Research and development expense for the three months ended December 31, 2022 was $1.0 million compared to $0.5 million for the three months ended December 31, 2021, an increase of $0.5 million, which was a result of an increase in NMB clinical trial costs of $0.9 million, partially offset by a decrease in personnel costs of $0.3 million.
Selling, general and administrative expenses for the three months ended December 31, 2022 were $2.1 million, of which $0.2 million was attributable to selling expense and $1.9 million was attributable to general and administrative expense. This compares to $11.5 million for the same prior year period, of which $6.5 million was attributable to selling expense and $5.0 million was attributable to general and administrative expense. Selling expenses decreased $6.3 million, primarily as a result of a reduction in personnel costs of $4.4 million, a decrease in marketing costs of $1.6 million and a decrease in associated travel expenses of $0.3 million. The decrease of $3.1 million in general and administrative costs was primarily a result of a decrease in personnel costs of $2.2 million, a decrease in public company costs of $0.5 million and a decrease in both consulting costs and travel expenses of $0.2 million.
As a result of the discontinuation of commercialization of ANJESO, Baudax Bio evaluated the intangible asset carrying value attributed to ANJESO as of December 31, 2022 and recorded a non-cash impairment loss of $1.9 million to eliminate the carrying value of the asset. The value of its construction in progress related to the construction of an additional manufacturing suite for ANJESO was further reduced by $0.5 million.
Baudax Bio reported net loss of $9.2 million, or $(12.33) per share, including non-cash charges of $6.1 million (primarily related to the inventory reserve expense discussed above), for the three months ended December 31, 2022. Adjusted net loss* was $3.1 million for the three months ended December 31, 2022. Net income for the three months ended December 31, 2021 was $29.4 million, or $437.19 per diluted share, including a non-cash benefit of $41.3 million. Adjusted net loss* was $11.9 million for the three months ended December 31, 2021.
Financial Results for the Year Ended December 31, 2022
Net product revenue related to sales of ANJESO in the U.S., recognized according to U.S. GAAP, for the year ended December 31, 2022 was $1.3 million. This compares to $1.1 million for the year ended December 31, 2021, an increase of $0.2 million, which was attributable to increased demand at existing accounts. While utilizing the title model of distribution, product revenue was recognized as shipments were made to the Company’s third-party logistics provider.
Cost of sales for the year ended December 31, 2022 was $7.0 million, compared to $2.4 million for the year ended December 31, 2021, an increase of $4.6 million, and consisted of product costs, royalty expense and certain fixed costs associated with the manufacturing of ANJESO, including supply chain and quality costs. The increase of $4.6 million was primarily a result of the increase in the non-cash charge for inventory reserve expense of $5.2 million, partially offset by the reduction in personnel related costs of $0.4 million and the reduction in production and storage costs of $0.2 million. Certain product costs of ANJESO units recognized as revenue during the year ended December 31, 2022 and 2021 were expensed prior to the FDA approval of ANJESO in February 2020, and therefore are not included in cost of sales during the related periods.
Research and development expenses for the year ended December 31, 2022 were $3.9 million compared to $3.1 million for the year ended December 31, 2021. The increase of $0.8 million was primarily due to the increase in the NMB portfolio clinical trial costs of $1.0 million and an increase of $0.2 million related to the pediatric clinical trial costs for ANJESO. These costs were partially offset by a decrease in personnel related costs of $0.4 million.
Selling, general and administrative expenses for the year ended December 31, 2022 were $24.1 million, of which $9.4 million was attributable to selling expense and $14.7 million was attributable to general and administrative expense. This compares to $45.3 million for the same prior year period, of which $22.4 million was attributable to selling expense and $22.9 million was attributable to general and administrative expense. Selling expenses decreased $13.0 million, primarily as a result of a reduction in personnel costs of $7.9 million, a decrease in marketing costs of $4.7 million and a decrease in travel expenses of $0.4 million compared to 2021. The decrease of $8.2 million in general and administrative expenses was primarily a result of a decrease in personnel costs of $4.7 million, a decrease in public company costs of $2.3 million, a decrease in consulting costs of $0.9 million and a decrease in other costs of $0.3 million.
As a result of the discontinuation of commercialization of ANJESO, Baudax Bio evaluated the intangible asset carrying value attributed to ANJESO as of December 31, 2022 and recorded a non-cash impairment loss of $19.7 million to eliminate the carrying value of the asset. Additionally, the value of its construction in progress related to the construction of an additional manufacturing suite for ANJESO was reduced by $4.2 million.
Baudax Bio reported net loss of $58.8 million, or $(177.30) per share, including net non-cash charges of $30.9 million, for the year ended December 31, 2022. Adjusted net loss* was $27.9 million for the year ended December 31, 2022. For the year ended December 31, 2021 net loss was $19.8 million, or $(361.16) per share, including net non-cash benefit of $26.4 million. Adjusted net loss* was $46.2 million for the year ended December 31, 2021.
Non-GAAP Financial Measures
To supplement the Company’s financial results determined by U.S. generally accepted accounting principles (“GAAP”), the Company is reporting certain non-GAAP information for its business, including adjusted net loss. Adjusted net loss is net loss as determined under GAAP, excluding the changes in fair values of contingent consideration and warrant valuations, gain on extinguishment of debt, interest, depreciation, amortization, stock-based compensation, losses on impairment of construction in progress and intangible assets and the write off of inventory. The Company believes this non-GAAP financial measure is helpful in understanding its business as it is useful to investors in allowing for greater transparency of supplemental information used by management. This measure is used by investors, as well as management in assessing the Company’s performance. Non-GAAP financial measures should be considered in addition to, but not as a substitute for, reported GAAP results. Further, Non-GAAP financial measures, even if similarly titled, may not be calculated in the same manner by all companies, and therefore should not be compared. Please see the section of this press release titled “Reconciliation of GAAP to Non-GAAP Financial Measures” for a reconciliation of non-GAAP adjusted net loss to its most directly comparable GAAP measure.
About Baudax Bio
Baudax Bio is a pharmaceutical company focused on innovative products for hospital and related settings. The Company has a pipeline of innovative pharmaceutical assets including two clinical-stage, novel neuromuscular blocking (NMBs) agents, one undergoing a Phase II clinical trial and an additional unique NMB undergoing a dose escalation Phase I clinical trial, as well as a proprietary chemical reversal agent specific to these NMBs, which is currently undergoing nonclinical and manufacturing studies to prepare for an expected IND filing in the summer of 2023. For more information, please visit www.baudaxbio.com.
Forward Looking Statements
This press release contains forward-looking statements that involve risks and uncertainties. Such forward-looking statements reflect Baudax Bio’s expectations about its future performance and opportunities that involve substantial risks and uncertainties. When used herein, the words “anticipate,” “believe,” “estimate,” “may,” “upcoming,” “plan,” “target,” “goal,” “intend” and “expect” and similar expressions, as they relate to Baudax Bio or its management, are intended to identify such forward-looking statements. These forward-looking statements are based on information available to Baudax Bio as of the date of publication on this internet site and are subject to a number of risks, uncertainties, and other factors that could cause Baudax Bio’s performance to differ materially from those expressed in, or implied by, these forward-looking statements. These risks and uncertainties include, among other things, risks related to market, economic and other conditions, the ongoing economic and social consequences of the COVID-19 pandemic, Baudax Bio’s ability to advance its current product candidate pipeline through pre-clinical studies and clinical trials, Baudax Bio’s ability to raise future financing for continued development of its product candidates such as BX1000, BX2000 and BX3000, Baudax Bio’s ability to pay its debt and satisfy conditions necessary to access future tranches of debt, Baudax Bio’s ability to comply with the financial and other covenants under its credit facility, Baudax Bio’s ability to manage costs and execute on its operational and budget plans, Baudax Bio’s ability to achieve its financial goals; Baudax Bio’s ability to maintain listing on the Nasdaq Capital Market; and Baudax Bio’s ability to obtain, maintain and successfully enforce adequate patent and other intellectual property protection. These forward-looking statements should be considered together with the risks and uncertainties that may affect Baudax Bio’s business and future results included in Baudax Bio’s filings with the Securities and Exchange Commission at www.sec.gov. These forward-looking statements are based on information currently available to Baudax Bio, and Baudax Bio assumes no obligation to update any forward-looking statements except as required by applicable law.
To supplement the Company’s financial results determined by U.S. generally accepted accounting principles (“GAAP”), the Company has disclosed in the tables below the following non-GAAP information about adjusted net loss.
Adjusted net loss is net loss as determined under GAAP, excluding the changes in fair values of contingent consideration and warrant valuations, gain on extinguishment of debt, interest, depreciation, amortization, stock-based compensation, losses on impairment of construction in progress and intangible assets and the write off of inventory.
The Company believes that non-GAAP financial measures are helpful in understanding its business as it is useful to investors in allowing for greater transparency of supplemental information used by management. Adjusted net loss is used by investors, as well as management in assessing the Company’s performance. Non-GAAP financial measures should be considered in addition to, but not as a substitute for, reported GAAP results. Further, Non-GAAP financial measures, even if similarly titled, may not be calculated in the same manner by all companies, and therefore should not be compared.
Robert LeBoyer, Vice President, Research Analyst, Life Sciences , Noble Capital Markets, Inc.
Refer to the bottom of the report for important disclosures
Webinar. BIO (Biotechnology Innovation Organization, an industry group) sponsored a webinar titled, “Long COVID: What Will It Take To Accelerate Therapeutic Progress?” Speakers included officials from government, academia, and drug development companies to discuss the scientific basis of the condition, its public health implications, and its potential treatments. Presenting companies included Axcella Health (AXLA) and Tonix Pharmaceuticals (TNXP).
Long COVID Symptoms and Prevalence. The program began with how Long COVID became recognized as a condition, its incidence, and its patient population. Scientific presentations showed the biological effects of the SARS-CoV-2 virus on cells in the body, including the connection between Long COVID and other chronic conditions such as CFS/ME (chronic fatigue syndrome/myalgic encephalomyelitis). Symptoms and their duration can vary widely, including inflammation, fatigue, organ dysfunction, and reactivation of latent viral reservoirs. The presenters agreed that the range of symptoms and their variability will require numerous drugs.
Axcella Health Presented AXA1125. Chief Scientific Officer at Axcella Health, Dr. Margaret Koziel, presented the scientific basis for the use of AXA1125 in Long COVID, including its effects on inflammation, mitochondrial dysfunction, and fatigue. Data from the Phase 2a trial was presented, showing improvements in function, and biomarkers that correlate with reductions in inflammation and mitochondrial dysfunction. The design of the Phase 2b/3 trial was also presented.
Tonix Pharmaceuticals Presented Data From TNX-102 SL. Tonix is currently enrolling patients in its Phase 2 PREVAIL trial testing TNX-102 SL, sublingual cyclobenzaprine, in Long COVID. This trial is based on common symptoms with fibromyalgia and chronic fatigue syndrome, such as pain, fatigue, and insomnia. Projected enrollment is about 470 patients with a primary endpoint of change in daily pain score from baseline over the 14-week treatment period.
Conclusion. The BIO webinar speakers agreed that the high variability and large population would require several drugs to adequately treat patients. For Axcella, we believe the presentation could raise awareness of AXA1125 and its “Phase 2b/3 Ready” status, allowing it obtain trial funding through partnerships, government funding, or from investors. Tonix was able to present how TNX-102 SL overlaps with other pain syndromes and how it could treat symptoms, as well as to highlight its clinical milestones in the coming year.
Summary. BIO (Biotechnology Innovation Organization, and industry group) sponsored a webinar titled, “Long COVID: What Will It Take To Accelerate Therapeutic Progress?” Speakers included officials from government, academia, and drug development companies to discuss the scientific basis of the condition, its public health implications, and its potential treatments. Presenting companies included Axcella Health (AXLS) and Tonix Pharmaceuticals (TNXP).
The program began with the history of Long COVID, how it became recognized as a condition, and its prevalence. Scientific presentations discussed the SARS-CoV-2 viral infection and its effects on different organs, as well as the mechanisms of infection that lead to fatigue, cerebral effects (brain fog), and chronic pain. The speakers pointed out that the range and severity of symptoms can vary widely, making it likely that numerous drugs will be needed.
The overlap between Long COVID and other chronic conditions, such as CFS/ME (chronic fatigue syndrome/myalgic encephalomyelitis), was also discussed. The common features in these conditions were cited in the “National Research Action Plan on Long COVID”, published by the Department of Health and Human Services in August 2022.
Axcella Health Spoke About AXA1125. Chief Scientific Officer at Axcella Health, Dr. Margaret Koziel, presented the scientific basis for the use of AXA1125 in Long COVID, including its effect on inflammation, mitochondrial dysfunction, epithelial dysfunction, and fatigue. Data from the Phase 2a trial was presented, showing improvements in physical and mental function. These data included biomarkers that correlate with improvements in inflammation and mitochondrial function. The design of the Phase 2b/3 trial was also presented.
Tonix Pharmaceuticals Presented Data From TNX-102 SL. Tonix is currently enrolling patients in its Phase 2 PREVAIL trial testing TNX-102 SL, sublingual cyclobenzaprine, in Long COVID. This trial is based on common symptoms with fibromyalgia and chronic fatigue syndrome, such as pain, fatigue, and insomnia. Projected enrollment is about 470 patients with a primary endpoint of change in daily pain score from baseline over the 14-week treatment period.
TNX-102 SL showed positive results in its Phase 3 RELIEF study in fibromyalgia, although the confirmatory Phase 3 RALLY missed its primary endpoint. After analyzing the RALLY trial, the Phase 3 RESILIENT trial began. An interim analysis from the RESILIENT trial is expected in 2Q23.
Conclusion. The BIO webinar gave different perspectives on Long COVID and discussed different approaches to treatment. For Axcella, we believe the presentation could raise awareness of AXA1125 data and its “Phase 2b/3” ready status, allowing it obtain trial funding through partnerships, government funding, or from investors. For Tonix, presentations on the common features of Long COVID and chronic pain syndromes support the use of Tonix’s TNX-102 SL, and show how its Phase 2 PREVAIL clinical trial design could become an effective treatment.
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No two hearts beat alike. The size and shape of the heart can vary from one person to the next. These differences can be particularly pronounced for people living with heart disease, as their hearts and major vessels work harder to overcome any compromised function.
MIT engineers are hoping to help doctors tailor treatments to patients’ specific heart form and function, with a custom robotic heart. The team has developed a procedure to 3D print a soft and flexible replica of a patient’s heart. They can then control the replica’s action to mimic that patient’s blood-pumping ability.
The procedure involves first converting medical images of a patient’s heart into a three-dimensional computer model, which the researchers can then 3D print using a polymer-based ink. The result is a soft, flexible shell in the exact shape of the patient’s own heart. The team can also use this approach to print a patient’s aorta — the major artery that carries blood out of the heart to the rest of the body.
To mimic the heart’s pumping action, the team has fabricated sleeves similar to blood pressure cuffs that wrap around a printed heart and aorta. The underside of each sleeve resembles precisely patterned bubble wrap. When the sleeve is connected to a pneumatic system, researchers can tune the outflowing air to rhythmically inflate the sleeve’s bubbles and contract the heart, mimicking its pumping action.
The researchers can also inflate a separate sleeve surrounding a printed aorta to constrict the vessel. This constriction, they say, can be tuned to mimic aortic stenosis — a condition in which the aortic valve narrows, causing the heart to work harder to force blood through the body.
Doctors commonly treat aortic stenosis by surgically implanting a synthetic valve designed to widen the aorta’s natural valve. In the future, the team says that doctors could potentially use their new procedure to first print a patient’s heart and aorta, then implant a variety of valves into the printed model to see which design results in the best function and fit for that particular patient. The heart replicas could also be used by research labs and the medical device industry as realistic platforms for testing therapies for various types of heart disease.
“All hearts are different,” says Luca Rosalia, a graduate student in the MIT-Harvard Program in Health Sciences and Technology. “There are massive variations, especially when patients are sick. The advantage of our system is that we can recreate not just the form of a patient’s heart, but also its function in both physiology and disease.”
Rosalia and his colleagues report their results in a study appearing today in Science Robotics. MIT co-authors include Caglar Ozturk, Debkalpa Goswami, Jean Bonnemain, Sophie Wang, and Ellen Roche, along with Benjamin Bonner of Massachusetts General Hospital, James Weaver of Harvard University, and Christopher Nguyen, Rishi Puri, and Samir Kapadia at the Cleveland Clinic in Ohio.
Print and Pump
In January 2020, team members, led by mechanical engineering professor Ellen Roche, developed a “biorobotic hybrid heart” — a general replica of a heart, made from synthetic muscle containing small, inflatable cylinders, which they could control to mimic the contractions of a real beating heart.
Shortly after those efforts, the Covid-19 pandemic forced Roche’s lab, along with most others on campus, to temporarily close. Undeterred, Rosalia continued tweaking the heart-pumping design at home.
“I recreated the whole system in my dorm room that March,” Rosalia recalls.
Months later, the lab reopened, and the team continued where it left off, working to improve the control of the heart-pumping sleeve, which they tested in animal and computational models. They then expanded their approach to develop sleeves and heart replicas that are specific to individual patients. For this, they turned to 3D printing.
“There is a lot of interest in the medical field in using 3D printing technology to accurately recreate patient anatomy for use in preprocedural planning and training,” notes Wang, who is a vascular surgery resident at Beth Israel Deaconess Medical Center in Boston.
An Inclusive Design
In the new study, the team took advantage of 3D printing to produce custom replicas of actual patients’ hearts. They used a polymer-based ink that, once printed and cured, can squeeze and stretch, similarly to a real beating heart.
As their source material, the researchers used medical scans of 15 patients diagnosed with aortic stenosis. The team converted each patient’s images into a three-dimensional computer model of the patient’s left ventricle (the main pumping chamber of the heart) and aorta. They fed this model into a 3D printer to generate a soft, anatomically accurate shell of both the ventricle and vessel.
The team also fabricated sleeves to wrap around the printed forms. They tailored each sleeve’s pockets such that, when wrapped around their respective forms and connected to a small air pumping system, the sleeves could be tuned separately to realistically contract and constrict the printed models.
The researchers showed that for each model heart, they could accurately recreate the same heart-pumping pressures and flows that were previously measured in each respective patient.
“Being able to match the patients’ flows and pressures was very encouraging,” Roche says. “We’re not only printing the heart’s anatomy, but also replicating its mechanics and physiology. That’s the part that we get excited about.”
Going a step further, the team aimed to replicate some of the interventions that a handful of the patients underwent, to see whether the printed heart and vessel responded in the same way. Some patients had received valve implants designed to widen the aorta. Roche and her colleagues implanted similar valves in the printed aortas modeled after each patient. When they activated the printed heart to pump, they observed that the implanted valve produced similarly improved flows as in actual patients following their surgical implants.
Finally, the team used an actuated printed heart to compare implants of different sizes, to see which would result in the best fit and flow — something they envision clinicians could potentially do for their patients in the future.
“Patients would get their imaging done, which they do anyway, and we would use that to make this system, ideally within the day,” says co-author Nguyen. “Once it’s up and running, clinicians could test different valve types and sizes and see which works best, then use that to implant.”
Ultimately, Roche says the patient-specific replicas could help develop and identify ideal treatments for individuals with unique and challenging cardiac geometries.
“Designing inclusively for a large range of anatomies, and testing interventions across this range, may increase the addressable target population for minimally invasive procedures,” Roche says.
This research was supported, in part, by the National Science Foundation, the National Institutes of Health, and the National Heart Lung Blood Institute.
Symptoms of Long COVID, Like Multi-Site Pain, Fatigue and Insomnia, are the Hallmarks of Chronic Pain Syndromes Like Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME)
Event Co-Hosted by the Biotechnology Innovation Organization (BIO) and Solve M.E., an Advocacy Group for CFS/ME
CHATHAM, N.J., Feb. 22, 2023 (GLOBE NEWSWIRE) — Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a clinical-stage biopharmaceutical company, today announced that during a virtual event co-hosted by BIO and Solve M.E. titled, “Long COVID: What Will it Take to Accelerate Therapeutic Progress?”, Seth Lederman, M.D., President and Chief Executive Officer of Tonix Pharmaceuticals, presented emerging research describing the role of infections in triggering fibromyalgia or CFS/ME and other fibromyalgia-type illnesses, and discussed Tonix’s ongoing Phase 2 study of TNX-102 SL in fibromyalgia-type Long COVID. Symptoms of Long COVID, like multi-site pain, fatigue and insomnia, are the hallmarks of chronic pain syndromes like fibromyalgia and CFS/ME.
“The U.S. Department of Health and Human Services National Research Action Plan on Long COVID1, released in August 2022, addresses the overlap of Long COVID with CFS/ME, which, like fibromyalgia, is one of the overlapping chronic pain syndromes with central sensitization,” said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. “Furthermore, a recent survey2 found comparable pain, fatigue and function between Long COVID, fibromyalgia and CFS/ME.”
Enrollment continues in the Phase 2 PREVAIL study of TNX-102 SL as a potential treatment for patients with Long COVID syndrome whose symptoms overlap with fibromyalgia. PREVAIL is a randomized, double-blind, placebo-controlled study in the U.S. that is expected to enroll approximately 470 patients. One unblinded interim analysis is anticipated based on the first 50% of randomized participants.
1Department of Health and Human Services, Office of the Assistant Secretary for Health. 2022. National Research Action Plan on Long COVID, 200 Independence Ave SW, Washington, DC 20201.
2Haider S, et al. Pain. 2023;164(2):385-401.
About Solve M.E.
Solve M.E. is a non-profit organization that serves as a catalyst for critical research into diagnostics, treatments, and cures for CFS/ME, Long COVID and other post-infection conditions.
About BIO
BIO is the world’s largest advocacy association representing member companies, state biotechnology groups, academic and research institutions, and related organizations across the United States and in 30+ countries.
About Long COVID or Post-Acute Sequelae of SARS-CoV-2 (PASC)
Although most people recover from COVID-19 within weeks of the acute illness, a substantial portion develop a chronic syndrome called Long COVID. These individuals experience a constellation of symptoms long past the time of recovery from acute COVID-19. Most Long COVID patients who have been studied appear to have cleared the SARS-CoV-2 virus from their systems. The symptoms of Long COVID can include fatigue, sleep disorders, pain, fevers, shortness of breath, cognitive impairment described as “brain fog” or memory disturbance, gastrointestinal symptoms, anxiety, and depression. Long COVID can persist for months and can range in severity from mild to incapacitating. Several cohort studies have reported that persistence of symptoms following SARS-CoV-2 infection occurs in approximately 19% of people who recover from COVID.1 While typically associated with moderate or severe COVID-19, Long COVID can occur after mild COVID-19 or even after asymptomatic SARS-CoV-2 infection. Patients with Long COVID are sometimes referred to as “long-haulers”. Long COVID is a chronic disabling condition that is expected to result in a significant global health and economic burden.2 In response to the urgent need for therapies that address Long COVID, Congress awarded $1.15 billion to the National Institutes of Health to study Long COVID in December 2021.3 While the vaccines available in the U.S. under Emergency Use Authorization have been shown to prevent acute COVID, their ability to prevent Long COVID is unknown. There is currently no approved drug for the treatment of Long COVID.”
Tonix Pharmaceuticals Holding Corp.*
Tonix is a clinical-stage biopharmaceutical company focused on discovering, licensing, acquiring and developing therapeutics to treat and prevent human disease and alleviate suffering. Tonix’s portfolio is composed of central nervous system (CNS), rare disease, immunology and infectious disease product candidates. Tonix’s CNS portfolio includes both small molecules and biologics to treat pain, neurologic, psychiatric and addiction conditions. Tonix’s lead CNS candidate, TNX-102 SL (cyclobenzaprine HCl sublingual tablet), is in mid-Phase 3 development for the management of fibromyalgia with a new Phase 3 study launched in the second quarter of 2022 and interim data expected in the second quarter of 2023. TNX-102 SL is also being developed to treat Long COVID, a chronic post-acute COVID-19 condition. Tonix initiated a Phase 2 study in Long COVID in the third quarter of 2022. TNX-1300 (cocaine esterase) is a biologic designed to treat cocaine intoxication and has been granted Breakthrough Therapy designation by the FDA. A Phase 2 study of TNX-1300 is expected to be initiated in the second quarter of 2023. TNX-1900 (intranasal potentiated oxytocin), a small molecule in development for chronic migraine, is being studied in a potential pivotal Phase 2 study that initiated enrollment in the first quarter of 2023 and for which interim data is expected in the fourth quarter of 2023. TNX-601 ER (tianeptine hemioxalate extended-release tablets) is a once-daily formulation of tianeptine being developed as a potential treatment for major depressive disorder (MDD) with a Phase 2 study expected to be initiated in the first quarter of 2023. Tonix’s rare disease portfolio includes TNX-2900 (intranasal potentiated oxytocin) for the treatment of Prader-Willi syndrome. TNX-2900 has been granted Orphan Drug designation by the FDA. Tonix’s immunology portfolio includes biologics to address organ transplant rejection, autoimmunity and cancer, including TNX-1500, which is a humanized monoclonal antibody targeting CD40-ligand (CD40L or CD154) being developed for the prevention of allograft and xenograft rejection and for the treatment of autoimmune diseases. A Phase 1 study of TNX-1500 is expected to be initiated in the second quarter of 2023. Tonix’s infectious disease pipeline includes a vaccine in development to prevent smallpox and monkeypox, TNX-801; a next-generation vaccine to prevent COVID-19, TNX-1850; a platform to make fully human monoclonal antibodies to treat COVID-19, TNX-3600; and humanized anti-SARS-CoV-2 monoclonal antibodies, TNX-3800; and a class of broad-spectrum small molecule oral antivirals, TNX-3900. TNX-801, Tonix’s vaccine in development to prevent smallpox and monkeypox, also serves as the live virus vaccine platform or recombinant pox vaccine (RPV) platform for other infectious diseases. A Phase 1 study of TNX-801 is expected to be initiated in the second half of 2023.
*All of Tonix’s product candidates are investigational new drugs or biologics and have not been approved for any indication.
2Briggs, Andrew, and Anna Vassall. “Count the cost of disability caused by COVID-19.” (2021): 502-505.
3The NIH provision of Title III Health and Human Services, Division M–Coronavirus Response and Relief Supplemental Appropriations Act, 2021, of H.R. 133, The Consolidated Appropriations Act of 2021. The bill was enacted into law on 27 December 2020, becoming Public Law 116-260.
This press release and further information about Tonix can be found at www.tonixpharma.com.
Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Tonix’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Tonix does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2021, as filed with the Securities and Exchange Commission (the “SEC”) on March 14, 2022, and periodic reports filed with the SEC on or after the date thereof. All of Tonix’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof.
Schwazze (OTCQX:SHWZ, NEO:SHWZ) is building a premier vertically integrated regional cannabis company with assets in Colorado and New Mexico and will continue to take its operating system to other states where it can develop a differentiated regional leadership position. Schwazze is the parent company of a portfolio of leading cannabis businesses and brands spanning seed to sale. The Company is committed to unlocking the full potential of the cannabis plant to improve the human condition. Schwazze is anchored by a high-performance culture that combines customer-centric thinking and data science to test, measure, and drive decisions and outcomes. The Company’s leadership team has deep expertise in retailing, wholesaling, and building consumer brands at Fortune 500 companies as well as in the cannabis sector. Schwazze is passionate about making a difference in our communities, promoting diversity and inclusion, and doing our part to incorporate climate-conscious best practices.
Joe Gomes, Managing Director – Generalist Analyst, Noble Capital Markets, Inc.
Joshua Zoepfel, Research Associate, Noble Capital Markets, Inc.
Refer to the full report for the price target, fundamental analysis, and rating.
New Acquisitions. Continuing to build out its Colorado dispensary network, Schwazze has announced definitive documents to acquire certain assets of Cannabis Care Wellness Centers, LLC and Green Medicals Wellness Center #5, LLC (d/b/a “Smokey’s”). The proposed transaction includes the adult use Smokey’s dispensaries located at 2515 7th Avenue in Garden City as well as 5740 S. College Ave. in Fort Collins. These two vibrant cannabis markets have limited licenses and present Schwazze with more opportunities to serve customers in northern Colorado.
Details. The consideration for the proposed acquisition is $7.5 million and will be paid as $3.75M in cash and $3.75M in stock at closing. The acquisition is expected to close in the second quarter of 2023 after Colorado Marijuana Enforcement Division and local licensing approvals.
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*Analyst certification and important disclosures included in the full report. NOTE: investment decisions should not be based upon the content of this research summary. Proper due diligence is required before making any investment decision.
People Produce Endocannabinoids – Similar to Compounds Found in Marijuana – Critical to Many Bodily Functions
Over the past two decades, a great deal of attention has been given to marijuana – also known as pot or weed. As of early 2023, marijuana has been legalized for recreational use in 21 states and Washington, D.C., and the use of marijuana for medical purposes has grown significantly during the last 20 or so years.
But few people know that the human body naturally produces chemicals that are very similar to delta-9-tetrahydrocannabinol, or THC, the psychoactive compound in marijuana, which comes from the Cannabis sativa plant. These substances are called endocannabinoids, and they’re found across all vertebrate species.
Evolutionarily, the appearance of endocannabinoids in vertebrate animals predates that of Cannabis sativa by about 575 million years.
It is as if the human body has its own version of a marijuana seedling inside, constantly producing small amounts of endocannabinoids.
The similarity of endocannabinoids to THC, and their importance in maintaining human health, have raised significant interest among scientists to further study their role in health and disease, and potentially use them as therapeutic targets to treat human diseases.
THC was first identified in 1964, and is just one of more than 100 compounds found in marijuana that are called cannabinoids.
Endocannabinoids were not discovered until 1992. Since then, research has revealed that they are critical for many important physiological functions that regulate human health. An imbalance in the production of endocannabinoids, or in the body’s responsiveness to them, can lead to major clinical disorders, including obesity as well as neurodegenerative, cardiovascular and inflammatory diseases.
This article was republished with permission from The Conversation, a news site dedicated to sharing ideas from academic experts. It represents the research-based findings and thoughts of Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South Carolina and Mitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South Carolina.
We are immunologists who have been studying the effects of marijuana cannabinoids and vertebrate endocannabinoids on inflammation and cancer for more than two decades. Research in our laboratory has shown that endocannabinoids regulate inflammation and other immune functions.
What is the Endocannabinoid System?
A variety of tissues in the body, including brain, muscle, fatty tissue and immune cells, produce small quantities of endocannabinoids. There are two main types of endocannabinoids: anandamide, or AEA, and 2-arachidonoyl glycerol, known as 2-AG. Both of them can activate the body’s cannabinoid receptors, which receive and process chemical signals in cells.
One of these receptors, called CB1, is found predominantly in the brain. The other, called CB2, is found mainly in immune cells. It is primarily through the activation of these two receptors that endocannabinoids control many bodily functions.
The receptors can be compared to a “lock” and the endocannabinoids a “key” that can open the lock and gain entry into the cells. All these endocannabinoid receptors and molecules together are referred to as the endocannabinoid system.
The cannabis plant contains another compound called cannabidiol, or CBD, which has become popular for its medicinal properties. Unlike THC, CBD doesn’t have psychoactive properties because it does not activate CB1 receptors in the brain. Nor does it activate the CB2 receptors, meaning that its action on immune cells is independent of CB2 receptors.
Endocannabinoid receptors are found throughout most of the human body
Role of Endocannabinoids in the Body
The euphoric “high” feeling that people experience when using marijuana comes from THC activating the CB1 receptors in the brain.
But when endocannabinoids activate CB1 receptors, by comparison, they do not cause a marijuana high. One reason is that the body produces them in smaller quantities than the typical amount of THC in marijuana. The other is that certain enzymes break them down rapidly after they carry out their cellular functions.
However, there is growing evidence that certain activities may release mood-elevating endocannabinoids. Some research suggests that the relaxed, euphoric feeling you get after exercise, called a “runner’s high,” results from the release of endocannabinoids rather than from endorphins, as previously thought.
The endocannabinoids regulate several bodily functions such as sleep, mood, appetite, learning, memory, body temperature, pain, immune functions and fertility. They control some of these functions by regulating nerve cell signaling in the brain. Normally, nerve cells communicate with one another at junctions called synapses. The endocannabinoid system in the brain regulates this communication at synapses, which explains its ability to affect a wide array of bodily functions.
The Elixir of Endocannabinoids
Research in our laboratory has shown that certain cells of the immune system produce endocannabinoids that can regulate inflammation and other immune functions through the activation of CB2 receptors.
In addition, we have shown that endocannabinoids are highly effective in lessening the debilitating effects of autoimmune diseases. These are diseases in which the immune system goes haywire and starts destroying the body’s organs and tissues. Examples include multiple sclerosis, lupus, hepatitis and arthritis.
Recent research suggests that migraine, fibromyalgia, irritable bowel syndrome, post-traumatic stress disorder and bipolar disease are all linked to low levels of endocannabinoids.
In a 2022 study, researchers found that a defect in a gene that helps produce endocannabinoids causes early onset of Parkinson’s disease. Another 2022 study linked the same gene defect to other neurological disorders, including developmental delay, poor muscle control and vision problems.
Other research has shown that people with a defective form of CB1 receptors experience increased pain sensitivity such as migraine headaches and suffer from sleep and memory disorders and anxiety.
The endocannabinoid system – consisting of the endocannabinoids and the cannabinoid receptors – regulates nerve cell communication at the synapse, thereby playing a role in a variety of bodily functions.
The Likeness Between Marijuana and Endocannabinoids
We believe that the medicinal properties of THC may be linked to the molecule’s ability to compensate for a deficiency or defect in the production or functions of the endocannabinoids.
For example, scientists have found that people who experience certain types of chronic pain may have decreased production of endocannabinoids. People who consume marijuana for medicinal purposes report significant relief from pain. Because the THC in marijuana is the cannabinoid that reduces pain, it may be helping to compensate for the decreased production or functions of endocannabinoids in such patients.
Deciphering the role of endocannabinoids is still an emerging area of health research. Certainly much more research is needed to decipher their role in regulating different functions in the body.
In our view, it will also be important to continue to unravel the relationship between defects in the endocannabinoid system and the development of various diseases and clinical disorders. We think that the answers could hold great promise for the development of new therapies using the body’s own cannabinoids.
