Tag: Biotech

Investing in the Development of Cancer Drugs May be Considered Defensive

Posted on by phoffman@channelchek.com
Image: Visualization of a cancer cell (nucleus in blue) treated with bi-modular fusion proteins (BMFPs). BMFPs bind to an antigen on the surface of the cancer cell to be destroyed. – Inserm (Flickr)

Understanding the Cancer Treatment and Therapy Segments of Biotech

Transforming research discoveries into new cancer treatments takes investment in time and capital. But no one would argue that the end goals of this healthcare (biotech and pharma) sector are not worth it. Investing in the future of treating tumors, and preventing cancer growth is obviously rewarding from the human standpoint of saving life, but breakthroughs in oncology themselves could provide an investor that understands some of the more promising companies, oversized portfolio rewards. It goes without saying, knowledge and understanding of many companies at different stages of research and development, help the odds of being invested in successful stocks.  

Exploding Growth

According to a report by Grand View Research published in early last year, the global oncology drugs market size was valued at $135.7 billion in 2021 and is expected to grow at a compound annual growth rate (CAGR) of 8.3% from 2022 to 2028. The increasing prevalence of cancer, the rising geriatric population, and advancements in drug development and treatment modalities are some of the key factors driving the growth of the novel oncology drugs market.

Relief managing the side effects of treatments, especially chemotherapy, without opiods is also a part of this market. Changing treatment modalities, and growing demand for personalized medicine is still relatively new, and creating more growth opportunities. In addition, a continuing trend of mergers and acquisitions from pharmaceutical companies to expand their oncology drug pipelines and portfolios plays a part in the growth of this sector.  

Meet the management of Onconova (ONTX) in NY,NY for lunch on March 28. This is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. To request attendance, click the registration link here.

Where to Explore Cancer Treatment/Therapy Companies

Investors use Channelchek as one of their trusted outlets to discover and explore smaller public companies involved in oncology treatments and therapies. Below are five companies with a wealth of information housed on the platform. This includes high quality research and video content. For an expanded list of companies, a simple search on Channelchek under “Oncology” or “Cancer” will provide a wealth of more opportunities to discover.

Worth a Deeper Dive?

Onconova Therapeutics Inc. (ONTX) is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. It has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation. Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in two separate and complementary Phase 1 dose-escalation and expansion studies. These trials are currently underway in the United States and China. Onconova’s product candidate rigosertib is being studied in an investigator-sponsored study program, including in a dose-escalation and expansion Phase 1/2a investigator-sponsored study with oral rigosertib in combination with nivolumab for patients with KRAS+ non-small cell lung cancer. For more information, please visit www.onconova.com.

Onconova has a roadshow scheduled on March 28 in Manhattan, NY. More information on attending the lunch is available here.

Genprex, Inc. (GNPX) is a clinical-stage gene therapy company focused on developing therapies for patients with cancer and diabetes. Its technologies are designed to administer disease-fighting genes to provide new therapies for populations with cancer and diabetes who currently have limited treatment options. Genprex works with world-class institutions and collaborators to develop drug candidates to further its pipeline of gene therapies in order to provide novel treatment approaches. Genprex’s oncology program utilizes its proprietary, non-viral ONCOPREX® Nanoparticle Delivery System, which the Company believes is the first systemic gene therapy delivery platform used for cancer in humans. ONCOPREX encapsulates the gene-expressing plasmids using lipid nanoparticles. The resultant product is administered intravenously, where it is then taken up by tumor cells that express tumor suppressor proteins that are deficient in the body. The Company’s lead product candidate, REQORSA™ (quaratusugene ozeplasmid), is being evaluated as a treatment for non-small cell lung cancer (NSCLC) (with each of these clinical programs receiving a Fast Track Designation from the Food and Drug Administration) and for small cell lung cancer. Genprex’s diabetes gene therapy approach is comprised of a novel infusion process that uses an endoscope and an adeno-associated virus (AAV) vector to deliver Pdx1 and MafA genes to the pancreas. In models of T1D, the genes express proteins that transform alpha cells in the pancreas into functional beta-like cells, which can produce insulin but are distinct enough from beta cells to evade the body’s immune system. In T2D, where autoimmunity is not at play, it is believed that exhausted beta cells are also rejuvenated and replenished.

In 2022 Genprex was one of the more popular presenters at the NobleCon investor conference. A video replay of its presentation is available here.

Imugene Ltd. (IUGNF) is a clinical stage immuno-oncology company developing a range of new and novel immunotherapies that seek to activate the immune system of cancer patients to treat and eradicate tumours. Our unique platform technologies seek to harness the body’s immune system against tumours, potentially achieving a similar or greater effect than synthetically manufactured monoclonal antibody and other immunotherapies. Our product pipeline includes multiple immunotherapy B-cell vaccine candidates and an oncolytic virotherapy (CF33) aimed at treating a variety of cancers in combination with standard of care drugs and emerging immunotherapies such as CAR T’s for solid tumours. We are supported by a leading team of international cancer experts with extensive experience in developing new cancer therapies with many approved for sale and marketing for global markets.

For more data and information, visit immunogen on Channelchek.

MAIA Biotechnology Inc. (MAIA)  is a targeted therapy, immuno-oncology company focused on the development and commercialization of potential first-in-class drugs with novel mechanisms of action that are intended to meaningfully improve and extend the lives of people with cancer. Our lead program is THIO, a potential first-in-class cancer telomere targeting agent in clinical development for the treatment of NSCLC patients with telomerase-positive cancer cells. Noble Capital Markets initiated coverage of MAIA on February 21, 2023. A copy of the report can be found here.

PDS Biotechnology Corporation (PDSB) is a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer and infectious disease immunotherapies based on our proprietary Versamune® and Infectimune™ T cell-activating technology platforms. We believe our targeted Versamune® based candidates have the potential to overcome the limitations of current immunotherapy by inducing large quantities of high-quality, potent polyfunctional tumor specific CD4+ helper and CD8+ killer T cells. To date, our lead Versamune® clinical candidate, PDS0101, has demonstrated the potential to reduce tumors and stabilize disease in combination with approved and investigational therapeutics in patients with a broad range of HPV-positive cancers in multiple Phase 2 clinical trials. Our Infectimune™ based vaccines have also demonstrated the potential to induce not only robust and durable neutralizing antibody responses, but also powerful T cell responses, including long-lasting memory T cell responses in pre-clinical studies to date. To learn more, please visit www.pdsbiotech.com or follow us on Twitter at @PDSBiotech.

As part of the Channelchek TakeAway Series, Senior Life Sciences Analyst, Robert LeBoyer sat down with management and discussed PDS Bio, listen to the discussion, including questions from the audience here.

Take Away

In the investment arena, oncology is a growing part of the healthcare sector, specifically the biotechnology and pharmaceutical segments. Companies that develop and market oncology drugs or provide related services are viewed as uncorrelated to other sectors. The demand for the next generation of improved treatments is expected to be ongoing.  While the approval process and regulatory bottlenecks of biotech are unlike any other product category, there are many reasons to review and consider this largely uncorrelated sector – then  dig deeper to possibly cancer R &D.

For the smaller companies considered to have the most potential, a good starting point is Channelchek where you’ll find articles, research, videos, and data, all in one place.

Paul Hoffman

Managing Editor, Channelchek

Sources

https://www.marketwatch.com/press-release/oncology-drugs-market-share-and-forecast-till-2028-2023-03-20

https://investingnews.com/daily/life-science-investing/biotech-investing/top-oncology-companies/

Biotech Announcement Sends Stock Up 258%

Posted on by phoffman@channelchek.com
Image Credit: Bradley Johnson (Flickr)

The Power of Small Companies Highlighted in Today’s Biopharma Announcements

Business headlines surrounding Silicon Valley Bank and its customers may take some time to fade from the front page. In the meantime, looking past them, there are some positive news and developments. Two news items involve announcements by biotech/pharmaceutical companies this week. One is a deal you don’t have to dig too deep to find, Pfizer (PFE), the pharmaceutical behemoth, is looking to acquire Seagen (SGEN) for $43 billion. The second is a smaller deal and has been crowded off many newsfeeds. Provention Bio (PRVB) is expected to be purchased by Sanofi (SNY) a large French-based pharmaceutical company.

Seagen shares increased 17% in the first hour of trading after the Pfizer announcement, shares of Provention were up 258% the same morning after the Sanofi announcement. Below is a chart of the month-to-date performance of the two that are to be acquired.

Source: Koyfin

The Power of Flying Below the Radar

Seagen is a borderline household name and has been a known acquisition target for some time. Just last July, Merck offered 40 billion for the company, this known interest in the company has kept the price elevated. Shifting the focus on the power of smaller, less talked about companies, they often have more potential for larger gains because they are less known. And while the numbers ($43 billion vs $2.9 billion) don’t make for compelling headlines, the numbers in the graph above demonstrate the impact can be far more compelling to investors.

The Provention Bio Deal

Sanofi and Provention Bio, a U.S.-based, publicly traded biopharmaceutical company focused on preventing autoimmune diseases, including type 1 diabetes (T1D), entered into an agreement for Sanofi to acquire Provention Bio, Inc., for $25.00 per share in cash.

Under the terms of the agreement, Sanofi will begin a cash tender offer to acquire all outstanding shares of Provention Bio.

The actual completion of the tender is subject to standard conditions, including the tendering of a number of shares of Provention Bio, Inc. common stock that, together with shares already owned by Sanofi or its affiliates, represents at least a majority of the outstanding shares of Provention Bio, Inc. common stock.

If the tender offer is successfully completed, then a wholly owned subsidiary of Sanofi will merge with and into Provention Bio, Inc., and all of the outstanding Provention shares that are not tendered in the offer will be converted into the right to receive the same $25.00 per share in cash offered to Provention Bio, Inc. shareholders as part of the offer. Sanofi plans to fund the transaction with available cash. Subject to the satisfaction or waiver of customary closing conditions, Sanofi expects to complete the acquisition in the second quarter of 2023.

Worth Noting

The largest pharmaceutical companies developed huge cash “war chests” during the pandemic era. While they are prudent and tactical when deciding to grow through acquisition, the earnings on much of their cash stockpiles relative to inflation may be erosive to the pool’s purchasing power. Additionally, many small pharmaceutical and biotech companies that are developing tomorrow’s next wonder drugs are short the cash they need to drive their R&D to the finish line, and then to market. It’s presumed these companies are quietly being reviewed for a possible fit by big pharma. Big pharma’s current patents are also being eroded by time as each day they approach patent expiration. This is added incentive for these large companies to be actively looking for future merger and acquisition targets.

Smaller companies, for their part want their progress and potential more known. It is only through being known, and the more broadly the better, that investors of all types understand the work they do and the potential along with the risk they hold. These companies often hire the service of impartial, highly credible equity analysts to provide details of the pipeline and the successes and challenges of the company. This company-sponsored research provides investors with a third-party window into the company. The window is, at times, as basic as the idea that investors need to know enough about the existence of a small company to want to own shares. Greater investor interest typically increases liquidity which could help the company continue moving forward and developing its products.

Channelchek houses quality company-sponsored research. For Life Sciences company-sponsored research covered by FINRA licensed Sr. Analyst Robert LeBoyer visit this link. For Healthcare Services Sr. Analyst Gregory Aurand visit this link.

Paul Hoffman

Managing Editor, Channelchek

What to Look for in a Biotech Stock

Posted on by phoffman@channelchek.com
Image Credit: Marco Verch (Flickr)

Steps to Discover Which Biotech Stocks May Get Hot

The biotech sector is in and of itself exciting. A company developing an idea that can improve human lives, decrease suffering, or even prevent death, by nature, could be a more rewarding endeavor than investing in a company that, by comparison, does little to make a big difference. If, at the same time, the opportunity to return the investor a multiple over returns available elsewhere in the market, then the motivation to allocate a portion of investment capital increases dramatically. But how does an investor gauge a company in the biotech sector and evaluate its chance of survival and likelihood of success?

As with much of investing, sure things don’t often provide a good return. And adding risk doesn’t necessarily equate to added return. The higher perceived risk of a sector such as biotech needs to be offset by research. Filtering stocks through a selection process is key, so the probability of picking those that survive and thrive is higher than average.

I spoke with Robert LeBoyer, the Senior Life Sciences Analyst at Noble Capital Markets, and asked him to list factors to improve the likelihood of choosing a successful biotech company. His knowledge and enthusiasm for the sector caused me to want to share what I learned.

Differentiation

Companies developing a drug that is different than all that came before for what it proposes to treat or prevent stand a good chance of getting funding to make it through the different phases of study. With a development time of 3-5 years, it is best if there is a clear unmet need for the therapy or no current therapies at all.

Investors should determine if there are treatments presently and ask whether the drug or treatment mechanism is a significant improvement over any current product. Also is the field crowded or will it soon be crowded with alternatives to what a company may bring to market? LeBoyer recommended asking where there is an improvement. He gave the example of many cholesterol-lowering drugs, which he said all target the same enzyme. A company with a drug that similarly targets that enzyme may not be worth exploring. Learning of a company that has a different mechanism of action, one which shows promise of greater efficacy, or, reduced cost, or fewer side effects may be worth exploring further.

As an example of a company that had met these criteria some years back, Gilead received approval for a once-daily tablet to treat hepatitis C. Prior to this, the only treatment options involved a year-long regimen of weekly interferon injections and ribavirin tablets. The side effects were depression, nausea, flu-like symptoms, and a reduction in some blood cells. The cost of the injections and treatments could cost a health insurer $1 million over the life of the patient. The Gilead treatment, which has a price tag of $93,000, is mathematically more cost-effective. The therapy which Gilead got approved in the U.S. in 2013 was a better treatment than what existed, and even better tolerated by patients. The stock went from $20 to $120 in about a years time after approval.

Development

Clinical development was another attribute brought up by Noble’s analyst. With even the best proof of concept or early-stage trial success, assessing the chance that clinical stage trials may fail for pipeline candidates is difficult.  This is why a company with a diverse pipeline with a number of products being developed or in later stages of clinical trials, increases the probability of successful biotech investment. Many companies easily pass stage one trials and even stage two, but don’t get past the final hurdle. LeBoyer shared with me a story of a company he now covers that had a vaccine for Covid-19 early on. The human clinical trials, however, were not done in the U.S., but were instead the result of trials on persons mostly of similar lineage. The FDA required a sampling comparable to the diversification of heritage or gene pool in the U.S.  

Obtaining a basic understanding of the FDA side of development is important for anyone making decisions on biotech stocks.

The drug approval process in the U.S. involves multi-layered (Step One through Step Four) with each representing an important milestone on the path to full approval so the product can be brought to market or meet rejection along the path.

Step One is the development phase, Step Two is research, Step Three is Clinical Trials, and Step Four is FDA Approval.

Knowing where companies stands in the FDA step process can help an investor assess the likelihood of approval. Many products, can get to the last step and not be approved, but those just starting out on Step One are a greater risk both in the time it will take and the chance for something to not be to the FDA’s liking.

Finances

Biotech companies, by and large burn through cash in their research, development and trial periods. Understanding how long the cash on hand and other available sources can last before they need to raise more cash, then comparing this with how close to an expected finish line they are, could help an investor steer away from a company that may have a product in the pipeline that meets other key elements investors should look at, but unfortunately, funds may stand in the way of success.

Robert LeBoyer explained that the current high-interest rate environment, coupled with depressed stock prices, makes this particularly important now. For those companies that can borrow, the cost of money is now far more expensive than it had been in the last decade and a half. And issuing more shares, essentially selling more of the company, dilutes the value of shares currently held. It could become a tricky situation that stockholders or those deciding to become a stockholder should monitor

Take Away

Are there companies with a pipeline that includes drugs that meet a large unmet need (as one example, Alzheimer’s), or can attack a disease like cancer in a unique way that would be embraced by the medical community and patients? “Unicorn” companies do exist, but finding them, assessing them, and doing it before a louder investment buzz occurs takes some digging. A solid place to start digging is under the biotech company section on Channelchek.  Available by clicking here, here investors are exposed to many opportunities and the underlying data, the latest news, and of course, thorough company descriptions.

Biotech companies covered by analyst Robert LeBoyer, along with his current research are available here. Channelchek will be highlighting interesting biotechs in future articles and discussing their work and status against the criteria presented above. Join Channelchek to receive emails and gain free access to these articles, video presentations, updated research reports, and news of company roadshows. Visit Rob LeBoyers coverage list here.

Paul Hoffman

Managing Editor, Channelchek

Was US Pharma Clinical Trial Activity Thwarted During the Pandemic?

Posted on by phoffman@channelchek.com
Image Source: NIH (Flickr)

The Volume Change of Non-Covid Related Medical Studies During the Pandemic

Did Covid19 related efforts by the pharmaceutical and biotech industry pull dollars from or impede the progression of non-Covid medical research? Also, were patient-enrolled studies significantly curtailed or paused during this period? Answers to these questions had been hard to quantify. Public estimates have ranged from the virus as having a minimal impact all the way to the other extreme of tragic decline. Applied Clinical Trials, an industry publication, has found a unique and accurate source from which to remove the guesswork and mine for a conclusion. From this, they were able to come to a definitive conclusion that surprised both extremes in expectations.

Statistical Sources

The US government’s Open Payments program is a national database that discloses payments made by drug and medical device companies to hospitals, physicians, and others in the health service provider field. The purpose of the data is to provide transparency; however, it has ample information to do analysis and provide conclusions on other questions related to clinical research or the broader medical arena.

Applied Clinical Trials discovered from Open Payments that the effect on the total volume of US clinical trial activity was quite limited. The statistics reveal that the overall pharmaceutical industry spending on all US patient enrollment and treatment activities did not decline in the years 2020 and 2021, from the year 2019, which was used as a baseline.

How the Data Was Used

The Open Payments database allowed direct measurement of the impact of COVID-19 on US industry-sponsored clinical trial activity through the end of 2021. More recent data is not yet available. The researchers learned Covid19 may have slowed and hindered the launch and execution of clinical trials in two ways. First, COVID-19 clinical trials may have displaced other clinical trial activity. Second, the Covid19 pandemic caused logistical and operational challenges to most clinical trials. Do you remember the six-foot rule? Recruiting patients, treating these patients, and validating source data are some of the areas where the pandemic created more than the normal amounts of hurdles for clinical trials.

The needed data was isolated by coding Open Payments by individual study indication. Also the U.S. National Library of Medicine (under the NIH) maintains the website clinicaltrials.gov. This website shows little or no decline in the number of US sites opened for Phase II and III clinical trials between 2019, 2020, and 2021. Of course open sites may reveal the amount of patient activity taking place. A Site may be opened, but have less patient activity. Therefore assessing actual activity levels from the ClinicalTrials.gov database is nt perfect. However, Open Payments provides more complete data since the payments are predominately tied to patient enrollment and treatment experienced.

Pharmaceutical company US clinical research spending, reported in Open Payments ($billions)

Overall Conclusion

The research shows there was no decline in non-COVID related study spending during the height of pandemic. Open Payments data show a constant, if undramatic, increase in US clinical trials between 2017 and 2021. Even when Covid19 related spending during the time period was removed, they saw no decline in study spending. Trials continued, through the period, at a rate that is similar to the year just prior to the start of the pandemic.

More About Open Payments

Open Payments is the result of a federal law, the Sunshine Act. Searches and downloads on the website are easy and may only be slowed by the size of many of the files. The data may not reach back beyond ten years because the site has only existed since late 2013. Since, pharmaceutical companies with at least one marketed product have been required to report payments to physicians and other medical professionals. These Open Payments include two types: general and research. General payments relate to pharmaceutical companies’ payments to medical professionals when marketed products are involved. Research payments are more restricted. They are broken down by clinical grant payments. These cover virtually all clinical investigators and their clinical trial experience across all indications.

Investor Take Away

Investors had been concerned that the pipeline at companies manufacturing medical devices and developing drugs, therapies, and other treatments may have a less full pipeline because of the pandemic and the US response to it. While the data doesn’t speak to the speed of the FDA approval process, it alleviates concerns that the related investment sectors were on hiatus and now behind on phase II and phase III trials.

Paul Hoffman

Managing Editor, Channelchek

Sources

https://www.appliedclinicaltrialsonline.com/view/the-limited-impact-of-covid-19-on-us-clinical-trial-activity

https://openpaymentsdata.cms.gov/

“Self-Boosting” Vaccines for a Myriad of Applications

Posted on by phoffman@channelchek.com
Image: Second Bay Studios

Microparticles Could be Used to Deliver “Self-Boosting” Vaccines

Anne Trafton | MIT News Office  

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.

Reprinted with permission from MIT News ( http://news.mit.edu/ )

3D-Printed Human Hearts (Patient Specific)

Posted on by phoffman@channelchek.com
Image Credit: Melanie Gonick, MIT

Custom, 3D-Printed Heart Replicas Look and Pump Just Like the Real Thing

Jennifer Chu | MIT News Office

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.

Reprinted with permission from MIT News ( http://news.mit.edu/ )

Cultivating a Microbiome that Reduces the Incidence of Cancer

Posted on by phoffman@channelchek.com
Image Credit: NIH (Flickr)

Microbes in Your Food Can Help or Hinder Your Body’s Defenses Against Cancer – How Diet Influences the Conflict Between Cell ‘Cooperators’ and ‘Cheaters’

The microbes living in your food can affect your risk of cancer. While some help your body fight cancer, others help tumors evolve and grow.

Gut microbes can influence your cancer risk by changing how your cells behave. Many cancer-protective microbes support normal, cooperative behavior of cells. Meanwhile, cancer-inducing microbes undermine cellular cooperation and increase your risk of cancer in the process.

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 Gissel Marquez Alcaraz, Ph.D. Student in Evolutionary Biology, Arizona State University and Athena Aktipis, Associate Professor of Psychology, Center for Evolution and Medicine, Arizona State University.

We are evolutionary biologists who study how cooperation and conflict occur inside the human body, including the ways cancer can evolve to exploit the body. Our systematic review examines how diet and the microbiome affect the ways the cells in your body interact with each other and either increase or decrease your risk of cancer.

Cancer is a Breakdown of Cell Cooperation

Every human body is a symphony of multicellular cooperation. Thirty trillion cells cooperate and coordinate with each other to make us viable multicellular organisms.

For multicellular cooperation to work, cells must engage in behaviors that serve the collective. These include controlled cell division, proper cell death, resource sharing, division of labor and protection of the extracellular environment. Multicellular cooperation is what allows the body to function effectively. If genetic mutations interfere with these proper behaviors, they can lead to the breakdown of cellular cooperation and the emergence of cancer.

Cancer cells can be thought of as cellular cheaters because they do not follow the rules of cooperative behavior. They mutate uncontrollably, evade cell death and take up excessive resources at the expense of the other cells. As these cheater cells replicate, cancer in the body begins to grow.

Cancer is fundamentally a problem of having multiple cells living together in one organism. As such, it has been around since the origins of multicellular life. This means that cancer suppression mechanisms have been evolving for hundreds of millions of years to help keep would-be cancer cells in check. Cells monitor themselves for mutations and induce cell death, also known as apoptosis, when necessary. Cells also monitor their neighbors for evidence of abnormal behavior, sending signals to aberrant cells to induce apoptosis. In addition, the body’s immune system monitors tissues for cancer cells to destroy them.

Cells that are able to evade detection, avoid apoptosis and replicate quickly have an evolutionary advantage within the body over cells that behave normally. This process within the body, called somatic evolution, is what leads cancer cells to grow and make people sick.

Microbes Can Help or Hinder Cell Cooperation

Microbes can affect cancer risk through changing the ways that the cells of the body interact with one another.

Some microbes can protect against cancer by helping maintain a healthy environment in the gut, reducing inflammation and DNA damage, and even by directly limiting tumor growth. Cancer-protective microbes like Lactobacillus pentosus, Lactobacillus gasseri and Bifidobacterium bifidum are found in the environment and different foods, and can live in the gut. These microbes promote cooperation among cells and limit the function of cheating cells by strengthening the body’s cancer defenses. Lactobacillus acidophilus, for example, increases the production of a protein called IL-12 that stimulates immune cells to act against tumors and suppress their growth.

Other microbes can promote cancer by inducing mutations in healthy cells that make it more likely for cellular cheaters to emerge and outcompete cooperative cells. Cancer-inducing microbes such as Enterococcus faecalis, Helicobacter pylori and Papillomavirus are associated with increased tumor burden and cancer progression. They can release toxins that damage DNA, change gene expression and increase the proliferation of tumor cells. Helicobacter pylori, for example, can induce cancer by secreting a protein called Tipα that can penetrate cells, alter their gene expression and drive gastric cancer.

Healthy Diet with Cancer-Protective Microbes

Because what you eat determines the amount of cancer-inducing and cancer-preventing microbes inside your body, we believe that the microbes we consume and cultivate are an important component of a healthy diet.

Beneficial microbes are typically found in fermented and plant-based diets, which include foods like vegetables, fruits, yogurt and whole grains. These foods have high nutritional value and contain microbes that increase the immune system’s ability to fight cancer and lower overall inflammation. High-fiber foods are prebiotic in the sense that they provide resources that help beneficial microbes thrive and subsequently provide benefits for their hosts. Many cancer-fighting microbes are abundantly present in fermented and high-fiber foods.

In contrast, harmful microbes can be found in highly-processed and meat-based diets. The Western diet, for example, contains an abundance of red and processed meats, fried food and high-sugar foods. It has been long known that meat-based diets are linked to higher cancer prevalence, and that red meat is a carcinogen. Studies have shown that meat-based diets are associated with cancer-inducing microbes including Fusobacteria and Peptostreptococcus in both humans and other species.

Microbes can enhance or interfere with how the body’s cells cooperate to prevent cancer. We believe that purposefully cultivating a microbiome that promotes cooperation among our cells can help reduce cancer risk.

A Good Place to Start to Evaluate Specific Biotech Companies?  

Posted on by phoffman@channelchek.com
Image Credit: Andrea Piacquadio (Pexels)

Exploring and Discovering Biotech Stocks

When it comes to hand-selecting companies for investment, a critical ingredient for success is information. This ingredient becomes even more critical with biotech companies. Each year, many companies have been involved in medicine, medical equipment, genetics, and wellness that take off and provide investors with double or triple-digit gains. During the same years, there are stocks in the sector that, on the surface seem to have just as much going for them, yet a diligent peak below the surface demonstrates their success is less probable.

The ability to get below the surface is one reason the JPMorgan Health Symposium draws between 8,000 and 10,000 attendees each year. Attending is an expensive commitment, but firsthand information, insights from others that are in-the-know, and exposure to scientific paths, trends and research that barely existed a few years earlier, can pay off.

If you were not among the 8,000 counted as attending at the 2023 JP Morgan Health Symposium, you’ll want to know, Noble Capital Markets, teamed with Channelchek to provide a video recap with insights and key takeaways on some of the biotech trends that may be worth exploring. This takeaway, coupled with select company presentations and questions from two top equity analysts in the field is sure to build on your current health sector knowledge.  Go Here For More Information (and free access).  

Trends Worth Exploring

Molecular diagnostics, involves taking DNA or RNA which is our unique and easily obtainable genetic code, and analyzing the sequences for red flags. These markers can pinpoint the chance for emergence of specific diseases. This field has expanded rapidly in recent years, with some products now being used regularly. But the potential is for far more to be developed and approved for use. This provides for tremendous profit potential.

Alternative pain relief, non-opioid and non-NAISD pain medications for chronic sufferers, could benefit millions who suffer eah day. The potential runs the gamut from chronic headaches or back pain to situations where one is recovering from surgery, sports injuries, or accidents. Millions of prescriptions are written each year for pain medications. This has, in part fed into the opioid crisis in the U.S. It has prompted an almost emergency-level need for replacing older addictive medications with effective alternatives.  There are a number of companies making gains in this area of great need.

Gene therapy is a technique to treat or cure disease by modifying one’s genes. In many cases, the hope is that it leads to a permanent cure. New gene therapies are being developed for a wide swath of ailments including life-threatening disease. It is expected to be in many cases the next generation of cure. The methods for gene therapy include replacing a disease-causing gene with a healthy copy, or inactivating the disease-causing gene. In other cases a modified gene may be introduced to help treat the disease. The research and development include cancers, infectious disease, organ failures, and autoimmune problems. Many of these companies will be opening the door to welcome life improvements for the some people, and curing what are now incurable diseases for others.

Drilling Down at the Company Level

It may feel uncomfortable to suggest that investing in and backing the right companies that resolve health issues can be profitable to you. But, the truth is, without investments and interest in stock ownership, tomorrow’s miracle drugs would never come to exist.

Watch the Takeaway from the JP Morgan conference with an eye toward what the company presenters deem important, and then listen to the analysts that also drill deeper beyond concept and stage of development, they discuss finances, which for many less experienced biotech investors, isn’t focused on enough. The companies selected for the Noble Capital Markets Takeaway all fall within one the fields mentioned above.  Register Here.

Possible Side-Effects

The J.P. Morgan Healthcare Symposium was held in mid-January. It is one of life science’s largest and most frenzied sharing of information related to the industry. Not everyone gets to go. We’re enthusiastic to be bringing you a slice of the excitement in hopes that you deepen your understanding of not just these companies, but what to look for in others as well.

Paul Hoffman

Managing Editor, Channelchek

Source

https://www.jpmorgan.com/solutions/cib/insights/health-care-conference

https://www.sfchronicle.com/sf/article/JPMorgan-health-care-conference-brings-8-000-to-17706261.php#:~:text=The%20JPMorgan%20health%20care%20conference%2C%20the%20largest%20industry,the%20first%20time%20since%202020%2C%20drawing%208%2C000%20attendees.

What’s Driving New Investor Interest in Biotech Stocks?

Posted on by phoffman@channelchek.com
Image: JP Morgan 41st Health Symposium

More Singles and Doubles for Investors in Biotech Expected (Few Home Runs)

Biotech has been highlighted by us a few times in recent weeks because of the potential the current financial dynamics could have for companies and investors. This past weekend, fresh out of the JP Morgan Health conference, a number of major publications have echoed a similar sentiment. A weekend piece in Barron’s in particular, caught my attention — its overall conclusion is the same as our readers have seen on Channelchek, but the path taken to get to the conclusion is somewhat different.

Health Landscape

From March 2020 until February 2021, biotech stocks were on a tear. The increase of 155%, as measured by the XBI, can be attributed to the intense focus on healthcare during the period.  Higher demand for anything healthcare-related drove share prices among the companies in this sector. This went a long way to provide capital to companies whose very nature are high costs and low revenue. The strength of the sector brought up the deserving, along with others that benefitted from biotech’s overall momentum.

The peak was nearly two years ago. Just as interest in biotech strengthened less than deserving companies, the weakness that followed has brought down many companies that would likely be valued much higher if not for the “throw the baby out with the bathwater” effect, especially with so many sector index fund investors.

This weakness must have been a painful transition for management of companies that are enthusiastic about the prospects of their research and development but now find they may be in survival mode and now spend more time pitching their story and plans while hoping for an overall rise in interest in the sector.

Biotech Mood 2023

The challenge for smaller biotech and medical device companies, which ordinarily spend many years developing products, while benefiting from few or none on the market, is that current valuations have made it a steeper uphill battle to raise new funds for their work and if they do, they may over dilute current shares.

There is a change in the mood of life sciences companies. the Barron’s article, titled, Tanking Biotech Stocks Will Mean a Big Year for Deals. Who Could Benefit? wrote, “With reality setting in, it’s a buyer’s market for companies looking for acquisitions and partnerships, according to the pharmaceutical and medical technology execs who gathered at the J.P. Morgan healthcare investor conference.” JP Morgan describes this annual event as the largest and most informative healthcare investment symposium in the industry. It connects global industry leaders, emerging fast-growth companies, innovative technology creators and members of the investment community.

The conference had been on hiatus for a couple of years in response to pandemic concerns. Certainly there was a lot of new and interesting information to be absorbed and understood.

An overall impression coming from this 41st health symposium is that management of the cash-starved small firms are in a situation where they either have to make a deal with a partner or acquirer or perish. The realization has set in that terms or prices they may have once been able to command are not today’s reality.

Geoff Martha , CEO of Medtronic (MDT), a medical device manufacturer, is quoted as telling Barron’s “We’re getting lots of calls from companies that literally we talked to six months ago.” He explained, back we’d offer, “we’ll buy you for X amount,” and the response would be, “No way, we’re worth [two times that].” The Medtronic CEO said they are now calling back trying to restart the conversations.

Source: Koyfin

Tide Turning

Speaking about the terms now expected, the chief financial officer of Gilead Sciences (GILD) is quoted as saying, “It’s changed completely in terms of both the deal structures they’ll contemplate, the valuations that they’re thinking about,”

Large pharmaceutical companies such as Gilead have the means to provide a non-dilutive source of funds; they are coming off a number of very profitable years and are looking for more rewarding uses of their cash. This doesn’t mean they are willing to cut large acquisition checks; the current trend seems to be more partnering deals – collaborations that keep the best ideas moving forward.

The risk-reward analysis by the large pharmaceutical companies is versus low-return financial assets on the balance sheet. “We can make a lot of investments because it’s not high cost,” says Anat Ashkenazi, CFO of Eli Lilly (LLY). “And we know some of these will fail, some will succeed. That’s how we operate.”

This has ushered in a health industry where large companies with cash to spend are capable of placing many well analyzed bets on future devices and drugs from small companies that now must make a deal or risk perishing.

Take Away

When a small biotech company gets an infusion of cash from collaborating with a big pharmaceutical company, its stock typically reacts very positively. This is not the same level of reaction as an outright purchase, but worthwhile just the same. There is an atmosphere where these partnerships and collaborations are likely to occur with more frequency. This could add to the number of small biotech stock potential winners early in 2023.

Discover Inner Details from the Health Symposium

Investors eager to discover more about the companies at the JPM conference, what was said, where the industry is going, and actionable investor possibilities, can immerse themselves in this info deeper next week.

Here’s how.

Noble Capital Markets’ equity analysts and investment bankers attended the meetings, lunches, cocktail events, and interviewed company management. Next week they will share their collective takeaways. It is perhaps better than having endured the unusually bad weather yourself in San Francisco, get more information here!

Paul Hoffman

Managing Editor, Channelchek

Sources

https://www.jpmorgan.com/solutions/cib/insights/health-care-conference

https://www.barrons.com/articles/biotech-partnerships-mergers-acquistions-51673643442

https://www.channelchek.com/news-channel/takeaway-series-on-channelchek-j-p-morgan-healthcare-conference

Organs-On-A-Chip Minimize Late-Stage Drug Development Failures

Posted on by phoffman@channelchek.com
Image: Lung-on-a-Chip,  National Center for Advancing Translational Sciences (Flickr)

Organ-On-A-Chip Models Allow Researchers to Conduct Studies Closer to Real-Life Conditions – and Possibly Grease the Drug Development Pipeline

Bringing a new drug to market costs billions of dollars and can take over a decade. These high monetary and time investments are both strong contributors to today’s skyrocketing health care costs and significant obstacles to delivering new therapies to patients. One big reason behind these barriers is the lab models researchers use to develop drugs in the first place.

Preclinical trials, or studies that test a drug’s efficacy and toxicity before it enters clinical trials in people, are mainly conducted on cell cultures and animals. Both are limited by their poor ability to mimic the conditions of the human body. Cell cultures in a petri dish are unable to replicate every aspect of tissue function, such as how cells interact in the body or the dynamics of living organs. And animals are not humans – even small genetic differences between species can be amplified to major physiological differences.

Fewer than 8% of successful animal studies for cancer therapies make it to human clinical trials. Because animal models often fail to predict drug effects in human clinical trials, these late-stage failures can significantly drive up both costs and patient health risks.

To address this translation problem, researchers have been developing a promising model that can more closely mimic the human body – organ-on-a-chip.

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 Chengpeng Chen, Assistant Professor of Chemistry and Biochemistry, University of Maryland, Baltimore County

As an analytical chemist, I have been working to develop organ and tissue models that avoid the simplicity of common cell cultures and the discrepancies of animal models. I believe that, with further development, organs-on-chips can help researchers study diseases and test drugs in conditions that are closer to real life.

What are Organs-On-Chips?

In the late 1990s, researchers figured out a way to layer elastic polymers to control and examine fluids at a microscopic level. This launched the field of microfluidics, which for the biomedical sciences involves the use of devices that can mimic the dynamic flow of fluids in the body, such as blood.

Advances in microfluidics have provided researchers a platform to culture cells that function more closely to how they would in the human body, specifically with organs-on-chips. The “chip” refers to the microfluidic device that encases the cells. They’re commonly made using the same technology as computer chips.

Not only do organs-on-chips mimic blood flow in the body, these platforms have microchambers that allow researchers to integrate multiple types of cells to mimic the diverse range of cell types normally present in an organ. The fluid flow connects these multiple cell types, allowing researchers to study how they interact with each other.

This technology can overcome the limitations of both static cell cultures and animal studies in several ways. First, the presence of fluid flowing in the model allows it to mimic both what a cell experiences in the body, such as how it receives nutrients and removes wastes, and how a drug will move in the blood and interact with multiple types of cells. The ability to control fluid flow also enables researchers to fine-tune the optimal dosing for a particular drug.

The lung-on-a-chip model, for instance, is able to integrate both the mechanical and physical qualities of a living human lung. It’s able to mimic the dilation and contraction, or inhalation and exhalation, of the lung and simulate the interface between the lung and air. The ability to replicate these qualities allows researchers to better study lung impairment across different factors.

Bringing Organs-On-Chips to Scale

While organ-on-a-chip pushes the boundaries of early-stage pharmaceutical research, the technology has not been widely integrated into drug development pipelines. I believe that a core obstacle for wide adoption of such chips is its high complexity and low practicality.

Current organ-on-a-chip models are difficult for the average scientist to use. Also, because most models are single-use and allow only one input, which limits what researchers can study at a given time, they are both expensive and time- and labor-intensive to implement. The high investments required to use these models might dampen enthusiasm to adopt them. After all, researchers often use the least complex models available for preclinical studies to reduce time and cost.

This chip mimics the blood-brain barrier. The blue dye marks where brain cells would go, and the red dye marks the route of blood flow. Vanderbilt University/Flickr

Lowering the technical bar to make and use organs-on-chips is critical to allowing the entire research community to take full advantage of their benefits. But this does not necessarily require simplifying the models. My lab, for example, has designed various “plug-and-play” tissue chips that are standardized and modular, allowing researchers to readily assemble premade parts to run their experiments.

The advent of 3D printing has also significantly facilitated the development of organ-on-a-chip, allowing researchers to directly manufacture entire tissue and organ models on chips. 3D printing is ideal for fast prototyping and design-sharing between users and also makes it easy for mass production of standardized materials.

I believe that organs-on-chips hold the potential to enable breakthroughs in drug discovery and allow researchers to better understand how organs function in health and disease. Increasing this technology’s accessibility could help take the model out of development in the lab and let it make its mark on the biomedical industry.

Biotech is Getting Investor’s Attention in a Big Way

Posted on by phoffman@channelchek.com
Image Credit: Patrick Foto(Flickr)

Well-Chosen Biotech Stocks Could Payoff Big for Investors

The Biotech sector has been flatlined since September but is now suddenly showing significant signs of life already in 2023. It’s only the second week of the new year, and already three US-based public small-cap companies are to be acquired by cash-rich drugmakers looking to expand their portfolios. The stocks of biotechs Albireo (ALBO), Amryt (AMYT), and CinCor (CINC) are all up between 93% and 140% after the announcements. A case can easily be made that the beaten-down biotech sector and the cash-rich pharmaceutical giants, with aging patents on their current drug portfolios, are going to find they are stronger together – this could be a huge win for investors.

Details of Recent Announcements

Ipsen (IPN), a French drug company, agreed to buy liver drug maker Albireo Pharma for at least $952 million, or $42 per share, plus another $10 per share if the FDA approves its Bylvay drug.

Italy’s Chisi Farmaceutici agree to pay up to $1.5 billion for Amryt Pharma. Amryt makes drugs for rare diseases. The agreement requires at least $14.50 per share, plus another $2.50 depending on milestones for its Filsuvez product, which treats a skin disease.

AstraZeneca, an Anglo-Swedish pharmaceutical company, said it’s paying up to $1.8 billion for CinCor Pharma, a maker of a blood pressure medication. The deal calls for $26 per share in cash, plus as much as another $10 per share if it’s able to make a Food and Drug Administration submission for a product based on baxdrostat drug in development for hypertension and chronic kidney disease.

The one thing in common between all three deals is an incentive for management to meet milestones which could include getting approval of late-stage drugs. Presumably, with the additional resources, these goals could become much easier for the companies that are allowing themselves to be acquired.

Will Other Acquisitions Follow?

Investors have learned all too well about investment bubbles, a situation where so much money flows into a sector that it becomes substantially overvalued. Then, when money isn’t flowing so freely, prices fall apart. But, the inverse of a bubble can also occur. A sector can be ignored for so long that investors don’t see value; when activity begins to perk up, many recognize value all at once and suddenly the sector is on fire. This inverse bubble may be at the earliest stages in small-cap biotech.

Source: Koyfin

“Smart Money” Investors Chasing Biotechs

In a story unrelated to the publicly traded companies being acquired, Reuters is reporting that private equity firms that had stayed uninvolved in what the firms believed to be the risk in the drug development business are now showing strong interest. “These firms are seeking to capitalize on the growing gap between the supply of capital for clinical research and the number of drugs competing for it, eight buyout executives and investors interviewed by Reuters said.”

The Reuters article highlights Blackstone (BX.N) as one company they explain is “leading the charge.” Carlyle is another investment group that, according to Reuters, is “now preparing to raise a dedicated life sciences fund,” the article explained the fund “could amass several billions of dollars, according to people familiar with the fundraising plans.” Reuters quoted Carlyle’s Global Head of healthcare as saying, “We are big believers in what we’ve called the biopharma revolution and in the explosion of discovery and science.”

These investment groups are not taking ownership in the companies they invest in, but rather a stake in clinical trials which stand a much greater chance with the injection of this new capital. The payoff arrangements are different for each deal.

What Should Self-Directed Investors Watch?

If there is a continued resurgence of activity among big pharma firms buying up publicly traded biotech firms, then small investors can expect to see more huge winners and, of course, others that never get off the ground. That is to say, while a few firms become the overnight 100% winners, many more languish and trade up and down without going any place. Increasing your chances of having at least one big winner among your holdings involves understanding the market, the companies, and the dynamics surrounding life sciences investments.

If you have already signed-up to have access to research and company information on Channelchek, then you have access to small-cap biotech stocks, and the research provided by the Senior Life Sciences Research Analyst at Noble Capital Markets. If you haven’t signed up, do this now by clicking here, and review the library of videos with interviews of management of biotechs and dig into the companies to learn where each is at in development and research.

Paul Hoffman

Managing Editor, Channelchek

Is There a Better Drug Patenting System?

Posted on by phoffman@channelchek.com
Image Credit: Alexandros Chatzidimos (Pexels)

Pharma’s Expensive Gaming of the Drug Patent System is Successfully Countered by the Medicines Patent Pool, Which Increases Global Access and Rewards Innovation

Biomedical innovation reached a new era during the COVID-19 pandemic as drug development went into overdrive. But the ways that brand companies license their patented drugs grant them market monopoly, preventing other entities from making generics so they can exclusively profit. This significantly limits the reach of lifesaving drugs, especially to low- and middle-income countries, or LMICs.

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 Lucy Xiaolu Wang, Assistant Professor of Resource Economics, UMass Amherst

Drug Patents in the Global Landscape

Patents are designed to provide incentives for innovation by granting monopoly power to patent holders for a period of time, typically 20 years from the application filing date.

However, this intention is complicated by strategic patenting. For example, companies can delay the creation of generic versions of a drug by obtaining additional patents based on slight changes to its formulation or method of use, among other tactics. This “evergreens” the company’s patent portfolio without requiring substantial new investments in research and development.

Furthermore, because patents are jurisdiction-specific, patent rights granted in the U.S. do not automatically apply to other countries. Firms often obtain multiple patents covering the same drug in different countries, adapting claims based on what is patentable in each jurisdiction.

To incentivize technology transfer to low- and middle-income countries, member nations of the World Trade Organization signed the 1995 Agreement on Trade-Related Aspects of Intellectual Property Rights, or TRIPS, which set the minimum standards for intellectual property regulation. Under TRIPS, governments and generic drug manufacturers in low- and middle-income countries may infringe on or invalidate patents to bring down patented drug prices under certain conditions. Patents in LMICs were also strengthened to incentivize firms from high-income countries to invest and trade with LMICs.

The 2001 Doha Declaration clarified the scope of TRIPS, emphasizing that patent regulations should not prevent drug access during public health crises. It also allowed compulsory licensing, or the production of patented products or processes without the consent of the patent owner.

One notable example of national patent law in practice after TRIPS is Novartis’ anticancer drug imatinib (Glivec or Gleevec). In 2013, India’s Supreme Court denied Novartis’s patent application for Glivec for obviousness, meaning both experts or the general public could arrive at the invention themselves without requiring much skill or thought. The issue centered on whether new forms of known substances, in this case a crystalline form of imatinib, were too obvious to be patentable. At the time, Glivec had already been patented in 40 other countries. As a result of India’s landmark ruling, the price of Glivec dropped from 150,000 INR (about US$2,200) to 6,000 INR ($88) for one month of treatment.

Patent Challenges and Pools

Although TRIPS seeks to balance incentives for innovation with access to patented technologies, issues with patents still remain. Drug cocktails, for example, can contain multiple patented compounds, each of which can be owned by different companies. Overlapping patent rights can create a “patent thicket” that blocks commercialization. Treatments for chronic conditions that require a stable and inexpensive supply of generics also pose a challenge, as the cost burden of long-term use of patented drugs is often unaffordable for patients in low- and middle-income countries.

One solution to these drug access issues is patent pools. In contrast to the currently decentralized licensing market, where each technology owner negotiates separately with each potential licensee, a patent pool provides a “one-stop shop” where licensees can get the rights for multiple patents at the same time. This can reduce transaction costs, royalty stacking and hold-up problems in drug commercialization.

Patent pools were first used in 1856 for sewing machines and were once ubiquitous across multiple industries. Patent pools gradually disappeared after a 1945 U.S. Supreme Court decision that increased regulatory scrutiny, hindering the formation of new pools. Patent pools were later revived in the 1990s in response to licensing challenges in the information and communication technology sector.

Patent pools create a one-stop shop for multiple patients, allowing multiple licensees to enter the market. Lucy Xiaolu Wang, CC BY-NC-ND

The Medicines Patent Pool

Despite many challenges, the first patent pool created for the purpose of promoting public health formed in 2010 with support from the United Nations and Unitaid. The Medicines Patent Pool, or MPP, aims to spur generic licensing for patented drugs that treat diseases disproportionately affecting low- and middle-income countries. Initially covering only HIV drugs, the MPP later expanded to include hepatitis C and tuberculosis drugs, many medications on the World Health Organization’s essential medicines list and, most recently, COVID-19 treatments and technologies.

But how much has the MPP improved drug access?

I sought to answer this question by examining how the Medicines Patent Pool has affected generic drug distribution in low- and middle-income countries and biomedical research and development in the U.S. To analyze the MPP’s influence on expanding access to generic drugs, I collected data on drug licensing contracts, procurement, public and private patents and other economic variables from over 100 low- and middle-income countries. To analyze the MPP’s influence on pharmaceutical innovation, I examined data on new clinical trials and new drug approvals over this period. This data spanned from 2000 to 2017.

The Medicines Patent Pool works as an intermediary between branded drug companies and generic licensees, increasing access to drugs. Lucy Xiaolu Wang, CC BY-NC-ND
i

I found that the MPP led to a 7% increase in the share of generic drugs supplied to LMICs. Increases were greater in countries where drugs are patented and in countries outside of sub-Saharan Africa, where baseline generic shares are lower and can benefit more from market-based licensing.

I also found that the MPP generated positive spillover effects for innovation. Firms outside the pool increased the number of trials they conducted on drug cocktails that included MPP compounds, while branded drug firms participating in the pool shifted their focus to developing new compounds. This suggests that the MPP allowed firms outside the pool to explore new and better ways to use MPP drugs, such as in new study populations or different treatment combinations, while brand name firms participating in the pool could spend more resources to develop new drugs.

The MPP was also able to lessen the burden of post-market surveillance for branded firms, allowing them to push new drugs through clinical trials while generic and other independent firms could monitor the safety and efficacy of approved drugs more cheaply.

Overall, my analysis shows the MPP effectively expanded generic access to HIV drugs in developing countries without diminishing innovation incentives. In fact, it even spurred companies to make better use of existing drugs.

Technology Licensing for COVID-19 and Beyond

Since May 2020, the Medicines Patent Pool has become a key partner of the World Health Organization COVID-19 Technology Access Pool, which works to spur equitable and affordable access to COVID-19 health products globally. The MPP has not only made licensing for COVID-19 health products more accessible to low- and middle-income countries, but also helped establish an mRNA vaccine technology transfer hub in South Africa to provide the technological training needed to develop and sell products treating COVID-19 and beyond.

Licensing COVID-19-related technologies can be complicated by the large amount of trade secrets involved in producing drugs derived from biological sources. These often require additional technology transfer beyond patents, such as manufacturing details. The MPP has also worked to communicate with brand firms, generic manufacturers and public health agencies in low- and middle-income countries to close the licensing knowledge gap.

Questions remain on how to best use licensing institutions like the MPP to increase generic drug access without hampering the incentive to innovate. But the MPP is proving that it is possible to align the interests of Big Pharma and generic manufacturers to save more lives in developing countries. In October 2022, the MPP signed a licensing agreement with Novartis for the leukemia drug nilotinib – the first time a cancer drug has come under a public health-oriented licensing agreement.

Scientists Uncover a Surprise in the Function of Essential Genes 

Posted on by phoffman@channelchek.com
Image Credit: National Human Research Institute (Flickr)

Scientists Unveil the Functional Landscape of Essential Genes

Nicole Davis | Whitehead Institute

A team of scientists at the Whitehead Institute for Biomedical Research and the Broad Institute of MIT and Harvard has systematically evaluated the functions of over 5,000 essential human genes using a novel, pooled, imaged-based screening method. Their analysis harnesses CRISPR-Cas9 to knock out gene activity and forms a first-of-its-kind resource for understanding and visualizing gene function in a wide range of cellular processes with both spatial and temporal resolution. The team’s findings span over 31 million individual cells and include quantitative data on hundreds of different parameters that enable predictions about how genes work and operate together. The new study appears in the Nov. 7 online issue of the journal Cell.

“For my entire career, I’ve wanted to see what happens in cells when the function of an essential gene is eliminated,” says MIT Professor Iain Cheeseman, who is a senior author of the study and a member of Whitehead Institute. “Now, we can do that, not just for one gene but for every single gene that matters for a human cell dividing in a dish, and it’s enormously powerful. The resource we’ve created will benefit not just our own lab, but labs around the world.”

Systematically disrupting the function of essential genes is not a new concept, but conventional methods have been limited by various factors, including cost, feasibility, and the ability to fully eliminate the activity of essential genes. Cheeseman, who is the Herman and Margaret Sokol Professor of Biology at MIT, and his colleagues collaborated with MIT Associate Professor Paul Blainey and his team at the Broad Institute to define and realize this ambitious joint goal. The Broad Institute researchers have pioneered a new genetic screening technology that marries two approaches — large-scale, pooled, genetic screens using CRISPR-Cas9 and imaging of cells to reveal both quantitative and qualitative differences. Moreover, the method is inexpensive compared to other methods and is practiced using commercially available equipment.

“We are proud to show the incredible resolution of cellular processes that are accessible with low-cost imaging assays in partnership with Iain’s lab at the Whitehead Institute,” says Blainey, a senior author of the study, an associate professor in the Department of Biological Engineering at MIT, a member of the Koch Institute for Integrative Cancer Research at MIT, and a core institute member at the Broad Institute. “And it’s clear that this is just the tip of the iceberg for our approach. The ability to relate genetic perturbations based on even more detailed phenotypic readouts is imperative, and now accessible, for many areas of research going forward.”

Cheeseman adds, “The ability to do pooled cell biological screening just fundamentally changes the game. You have two cells sitting next to each other and so your ability to make statistically significant calculations about whether they are the same or not is just so much higher, and you can discern very small differences.”

Cheeseman, Blainey, lead authors Luke Funk and Kuan-Chung Su, and their colleagues evaluated the functions of 5,072 essential genes in a human cell line. They analyzed four markers across the cells in their screen — DNA; the DNA damage response, a key cellular pathway that detects and responds to damaged DNA; and two important structural proteins, actin and tubulin. In addition to their primary screen, the scientists also conducted a smaller, follow-up screen focused on some 200 genes involved in cell division (also called “mitosis”). The genes were identified in their initial screen as playing a clear role in mitosis but had not been previously associated with the process. These data, which are made available via a companion website, provide a resource for other scientists to investigate the functions of genes they are interested in.

“There’s a huge amount of information that we collected on these cells. For example, for the cells’ nucleus, it is not just how brightly stained it is, but how large is it, how round is it, are the edges smooth or bumpy?” says Cheeseman. “A computer really can extract a wealth of spatial information.”

Flowing from this rich, multi-dimensional data, the scientists’ work provides a kind of cell biological “fingerprint” for each gene analyzed in the screen. Using sophisticated computational clustering strategies, the researchers can compare these fingerprints to each other and construct potential regulatory relationships among genes. Because the team’s data confirms multiple relationships that are already known, it can be used to confidently make predictions about genes whose functions and/or interactions with other genes are unknown.

There are a multitude of notable discoveries to emerge from the researchers’ screening data, including a surprising one related to ion channels. Two genes, AQP7 and ATP1A1, were identified for their roles in mitosis, specifically the proper segregation of chromosomes. These genes encode membrane-bound proteins that transport ions into and out of the cell. “In all the years I’ve been working on mitosis, I never imagined ion channels were involved,” says Cheeseman.

He adds, “We’re really just scratching the surface of what can be unearthed from our data. We hope many others will not only benefit from — but also build upon — this resource.”

This work was supported by grants from the U.S. National Institutes of Health as well as support from the Gordon and Betty Moore Foundation, a National Defense Science and Engineering Graduate Fellowship, and a Natural Sciences and Engineering Research Council Fellowship.

A team of scientists at the Whitehead Institute for Biomedical Research and the Broad Institute of MIT and Harvard has systematically evaluated the functions of over 5,000 essential human genes using a novel, pooled, imaged-based screening method. Their analysis harnesses CRISPR-Cas9 to knock out gene activity and forms a first-of-its-kind resource for understanding and visualizing gene function in a wide range of cellular processes with both spatial and temporal resolution. The team’s findings span over 31 million individual cells and include quantitative data on hundreds of different parameters that enable predictions about how genes work and operate together. The new study appears in the Nov. 7 online issue of the journal Cell.

“For my entire career, I’ve wanted to see what happens in cells when the function of an essential gene is eliminated,” says MIT Professor Iain Cheeseman, who is a senior author of the study and a member of Whitehead Institute. “Now, we can do that, not just for one gene but for every single gene that matters for a human cell dividing in a dish, and it’s enormously powerful. The resource we’ve created will benefit not just our own lab, but labs around the world.”

Systematically disrupting the function of essential genes is not a new concept, but conventional methods have been limited by various factors, including cost, feasibility, and the ability to fully eliminate the activity of essential genes. Cheeseman, who is the Herman and Margaret Sokol Professor of Biology at MIT, and his colleagues collaborated with MIT Associate Professor Paul Blainey and his team at the Broad Institute to define and realize this ambitious joint goal. The Broad Institute researchers have pioneered a new genetic screening technology that marries two approaches — large-scale, pooled, genetic screens using CRISPR-Cas9 and imaging of cells to reveal both quantitative and qualitative differences. Moreover, the method is inexpensive compared to other methods and is practiced using commercially available equipment.

“We are proud to show the incredible resolution of cellular processes that are accessible with low-cost imaging assays in partnership with Iain’s lab at the Whitehead Institute,” says Blainey, a senior author of the study, an associate professor in the Department of Biological Engineering at MIT, a member of the Koch Institute for Integrative Cancer Research at MIT, and a core institute member at the Broad Institute. “And it’s clear that this is just the tip of the iceberg for our approach. The ability to relate genetic perturbations based on even more detailed phenotypic readouts is imperative, and now accessible, for many areas of research going forward.”

Cheeseman adds, “The ability to do pooled cell biological screening just fundamentally changes the game. You have two cells sitting next to each other and so your ability to make statistically significant calculations about whether they are the same or not is just so much higher, and you can discern very small differences.”

Cheeseman, Blainey, lead authors Luke Funk and Kuan-Chung Su, and their colleagues evaluated the functions of 5,072 essential genes in a human cell line. They analyzed four markers across the cells in their screen — DNA; the DNA damage response, a key cellular pathway that detects and responds to damaged DNA; and two important structural proteins, actin and tubulin. In addition to their primary screen, the scientists also conducted a smaller, follow-up screen focused on some 200 genes involved in cell division (also called “mitosis”). The genes were identified in their initial screen as playing a clear role in mitosis but had not been previously associated with the process. These data, which are made available via a companion website, provide a resource for other scientists to investigate the functions of genes they are interested in.

“There’s a huge amount of information that we collected on these cells. For example, for the cells’ nucleus, it is not just how brightly stained it is, but how large is it, how round is it, are the edges smooth or bumpy?” says Cheeseman. “A computer really can extract a wealth of spatial information.”

Flowing from this rich, multi-dimensional data, the scientists’ work provides a kind of cell biological “fingerprint” for each gene analyzed in the screen. Using sophisticated computational clustering strategies, the researchers can compare these fingerprints to each other and construct potential regulatory relationships among genes. Because the team’s data confirms multiple relationships that are already known, it can be used to confidently make predictions about genes whose functions and/or interactions with other genes are unknown.

There are a multitude of notable discoveries to emerge from the researchers’ screening data, including a surprising one related to ion channels. Two genes, AQP7 and ATP1A1, were identified for their roles in mitosis, specifically the proper segregation of chromosomes. These genes encode membrane-bound proteins that transport ions into and out of the cell. “In all the years I’ve been working on mitosis, I never imagined ion channels were involved,” says Cheeseman.

He adds, “We’re really just scratching the surface of what can be unearthed from our data. We hope many others will not only benefit from — but also build upon — this resource.”

This work was supported by grants from the U.S. National Institutes of Health as well as support from the Gordon and Betty Moore Foundation, a National Defense Science and Engineering Graduate Fellowship, and a Natural Sciences and Engineering Research Council Fellowship.

Reprinted with permission from MIT News” ( http://news.mit.edu/ )