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BARDA looking for new antifungals/antibacterials in AMR fight
the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) within the US Department of Health and Human Services, has awarded Basilea an Other Transaction Agreement (OTA)...
Under the terms of the OTA, BARDA will support the development of designated novel, first-in-class antifungals and antibacterials in Basilea’s portfolio with a total potential non-dilutive funding of up to approximately USD 268 million over up to twelve years
[/qAbout invasive mold infections
Invasive aspergillosis and invasive infections with rare molds (e.g., Fusarium spp., Scedosporium spp., and Mucorales fungi) are life-threatening infections that predominantly affect immunocompromised patients, including patients with hematologic malignancies (blood cancer), transplant patients, or patients with other immunodeficiency disorders. These infections are associated with high morbidity and mortality.8, 9
About invasive candidiasis
Invasive candidiasis, including deep-seated tissue candidiasis and candidemia, is an increasingly important nosocomial infection, especially in patients hospitalized in intensive care units. Candida species are ranked as the fourth main cause of bloodstream infections in hospitals in the US.10 The prognosis of invasive candidiasis remains difficult, with a reported mortality rate for invasive candidiasis as high as 40%, even when patients receive antifungal therapy.11
In pre-clinical studies, Brilacidin shown to synergize with marketed antifungals against pathogenic species of aspergillosis, candidiasis, cryptococcosis and mucormycosis, and further exhibited potent stand-alone efficacy against Cryptococcus neoformans
· These data suggest Brilacidin has potential as a novel antifungal agent..
...the global antifungal drugs market estimated at $14.8 billion in 2021 and expected to reach $20.5 billion by 2030.
Antimicrobial resistance deaths could reach 39M 2025-2050
Doctors, scientists and public health experts have long warned of the potential consequences of worsening antimicrobial resistance, or AMR. It occurs when bacteria, fungi and pathogens evolve to withstand existing medications, including antibiotics, making them harder to kill...
They analyzed 520 million records from 204 countries and territories, including death certificates, hospital discharge documents and insurance claims. Then, they used statistical modeling to calculate deaths related to antimicrobial resistance from 1990 to 2021. They also made projections about how antimicrobial resistance would affect fatalities in the future... Developing new antibiotics will help tackle the problem, potentially averting millions of deaths, per the paper.
We urgently need new strategies to decrease the risk of severe infections through vaccines, new drugs, improved health care, better access to existing antibiotics and guidance on how to use them most effectively
Business history corroborates your focus on IPIX's science. As you noted:
R**n needed 18 years to find some one to buy a drug. Their first one failed.
'60 Minutes', in their April 28, 2024 segment, Nvidia's CEO noted that the company almost went bankrupt in 1997. Today, Nvidia is one of four companies with a greater than $2 Trillion market capitalization.
I like your favorite part of the abstract. But I LOVE my favorite part, which is the last line of the abstract.
We propose BRI as a new antifungal agent against cryptococcosis.
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Thanks for sharing that information that contradicts the often repeated falsehood that the company is "dead." My favorite part is "Brilicidin alone was shown to inhibit the growth of C. neoformans, acting as a fungicidal drug at concentrations of 2.5 µM, but surprisingly also potentiated the activity of CAS against this species. We have demonstrated that BRI is potentially an important antifungal agent against cryptococcosis, particularly important for synergizing with CAS, which is otherwise ineffective against this pathogen." https://www.biorxiv.org/content/10.1101/2024.04.10.588976v1.full
By year-end 2023, Cresemba was marketed in more than 70 countries, including the United States, most EU member states, China, Japan and countries in Latin America. According to the latest available market data, total global in-market sales of Cresemba in the twelve-month period between October 2022 and September 2023 amounted to USD 445 million, a 22 percent growth year-on-year.
About Cresemba (isavuconazole)
Basilea has entered into several license and distribution agreements for isavuconazole covering approximately 115 countries. In the 27 European Union member states, as well as in Iceland, Liechtenstein, Norway and the U.K., isavuconazole is approved for the treatment of adult patients with invasive aspergillosis and for adult patients with mucormycosis...
So Basilea has a drug, Cresemba, that is raking in $445M in annual global sales from asperillosis and mucormycosis.
In pre-clinical studies, Brilacidin shown to synergize with marketed antifungals against pathogenic species of aspergillosis, candidiasis, cryptococcosis and mucormycosis...
In cell culture, in Aspergillus fumigatus (A. fumigatus), Brilacidin converted CAS [caspofungin] from a fungistatic into a fungicidal drug, enabling it to overcome both drug resistance and biofilm formation...
In an A. fumigatus immunosuppressed mouse model in invasive pulmonary aspergillosis, Brilacidin plus CAS cleared infection in the lungs by almost 95 percent, compared to ~50 percent when each compound was administered individually. Brilacidin also showed in vitro an additive inhibitory effect when combined with POSA [posaconazole] in several species of Mucorales, the main etiological agents of mucormycosis...
In short, pre-clinical studies indicate that when brilacidin is combined with caspofungin and posaconazole it becomes highly-effective against aspergillosis and mucormycosis respectively.
We also know that the global market for drugs addressing aspergillosis and mucormycosis is at least $445M.
IPIX would be smart to be wary of any brilacidin deal with Basilea. IMO, they have a very strong motive ($445M) for keeping brilacidin from cannibalizing their sales in the aforementioned areas.
The antifungal drug market size is estimated to be $20.5B by 2030. Basilea is raking in $445M in marketing/licensing and distribution rights on this ONE drug. Just imagine what IPIX could be raking in with brilacidin showing good synergistic and standalone efficacy against multiple fungal indications.
Here are the major players in the antifungal drug market with whom IPIX could potentially negotiate marketing/licensing and distribution rights:
New Substance May Evade Antibiotic Resistance Like Brilacidin
Scientists have isolated a possible new antibiotic from a strain of bacterium found in sandy soil from North Carolina.
The way it works could make pathogens less likely to develop drug resistance.
The potent substance, called clovibactin, has only recently been discovered in the labs of the pharmaceutical start-up NovoBiotic. If it eventually proves safe, it will take about a decade to develop into something health practitioners can actually use.
Nevertheless, researchers behind the discovery are excited.
"I think this is the end of the road in the evolution towards resistance avoidance by antibiotics," states Northeastern University microbiologist Kim Lewis.
That's amazing to hear in the midst of a growing antimicrobial resistance crisis, which was the third leading global cause of death in 2019 and is expected to contribute to ten million deaths per year by 2050.
But there's reason to remain cautious in our optimism.
"We're at step one," notes Lewis. But "the most important thing about clovibactin, apart from its promise as a drug lead, is that it expands our understanding of antibiotics and what is possible."
Developing new antibiotics has proven challenging in part because 99 percent of bacteria species won't cooperatively grow in the lab.
Using a technique developed in previous work, Lewis and team took an isolate of sandy soil and extended its incubation period to see if this would encourage any new types of bacteria to grow in the lab. After three months the new species Eleftheria terrae carolina emerged.
From this the team isolated clovibactin.
"Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance," explains Utrecht University chemist Markus Weingarth.
Clovibactin parks itself on bacteria's innard-encasing envelope. Here, it collects and binds stringy fibrils of peptidoglycan molecules, which bacteria use to build the cell membrane on which it sits. The bacteria then destroy their own membrane in a futile attempt to eliminate this wormy hitchhiker.
"The most exciting thing is that it is unique and binds an extremely simple target (phosphate molecules) that cannot change," explains Lewis.
"This is the first discovery of a compound that binds a simple immutable target."
Because the phosphate part of the cell wall building molecule is crucial for the molecule to perform its function, the bacteria can't change the structure without consequences as they successfully do with other antibiotic target molecules. But this is just one way bacteria develop antibiotic resistance, so there are no guarantees.
Clovibactin has already cleared MRSA infections in mice and proved non-toxic to cultured human lab cells. The researchers did not detect the slightest hint of resistance during these experiments.
While there's still much to do, Shukla and colleague's research demonstrates the potential for at least long-effective antibiotics is very real.
There's also the POSITIVE trend of naysayers continually commenting on a stock they claim is dead in the water. IPIX has all kinds of favorable trends going for it and you are one of them.
Evolution is all about organisms and species adapting to their environment in order to survive. Historically, fungi haven't been a big problem in terms of human health because the normal human body temperature has, generally, been enough to kill most fungi. Global warming is killing a lot of fungi, but the fungi that remains is developing resistance to the normal human body temperature. Inside the human body they survive and cause all kinds of health problems.
While fungal diseases have devastated many animal and plant species, humans and other mammals have mostly been spared. That’s probably because mammals have body temperatures too warm for most fungi to replicate as well as powerful immune systems. But climate change may be challenging those defenses, bringing new fungal threats to human health, a microbiologist warns... Past work has shown a fungus can be coaxed to grow at warmer temperatures in a laboratory setting. “There are millions of fungal species out there,” Casadevall says. “As they adapt to a warmer climate, some of them will then have the capacity to breach our thermal defenses.
Brilacidin (IPIX), potentially, could be a major player in combatting the rise of fungal infections caused by climate change.
Extensive in vitro testing of Brilacidin by these research groups against multiple pathogenic human fungi has been completed. Across all pre-clinical studies conducted to date, Brilacidin has now exhibited varying degrees of inhibition against 13 of 19 “priority” fungal pathogens identified by the World Health Organization in need of novel treatments... ...Brilacidin showed potent stand-alone inhibition in multiple isolates of C. neoformans, for which few effective treatments exist... Brilacidin showed promising stand-alone inhibition as well in multiple isolates of Mucorales, Fusarium sp., C. glabrata, C. parapsilosis, C. guillermondii, Lomentospora prolificans, Scedosporium apiospermum, Blastomyces dermatitidis and Histoplasma capsulatum. USP researchers have also shown Brilacidin to be synergistic with caspofungin in different types of fungi. Additive effects were similarly observed in Brilacidin combinations with voriconazole and geldanamycin against A. fumigatus, as well as with posaconazole against Mucorales. Separate in vitro laboratory testing evaluating Brilacidin in combination with other conventional antifungals – including caspofungin, fluconazole, posaconazole, amphotericin B and micafungin – demonstrated additive or synergistic inhibition of fungal growth. Beyond Brilacidin’s broad-spectrum ability to directly inhibit fungal pathogens, Brilacidin may favorably modulate the host response to fungal infections.
The rise in deadly fungi caused by climate change, as well as the lack of effective drugs with which to combat this phenomena, is clearly a trend that's positive for IPIX. This also explains the worldwide interest in Brilacidin as an antifungal.
This is just another reason IPIX is a long-term hold. "The trend is your friend."
Climate-Change May Be Fueling Rise of Dangerous Fungi
"Humans and other mammals have warmer body temperatures than most fungal pathogens can tolerate, so have historically been protected from most [fungal] infections. However, rising temperatures can allow fungi to develop tolerance to warmer environments, and over time humans may lose resistance. Some researchers think this is what is already happening with Candida auris." https://www.cbsnews.com/news/candida-auris-climate-change-fungal-infection-rare/
Air Pollution Connected To Antibiotic Resistance Around World.
“By drawing a connection between PM2.5 pollution and the spread of antibiotic resistance, the paper expands our knowledge about the consequences of poor air quality. The extensive dataset used (over 11.5 million tested isolates) across 116 countries over nearly two decades lends considerable weight and validity to their findings. The usage of multiple predictors and a wide variety of sources for data collection suggests a comprehensive approach."
The amphiphilic nature of antimicrobial peptides can be mimicked by short arylamide foldamers, which have shown good efficacy and broad-spectrum antimicrobial activity with high selectivity for bacteria over eukaryotic cells. Resistance to this class of compounds, tested by using procedures applied to other compounds with the use of Staphylococcus aureus, did not develop.
The major component of the mechanism of action of arylamides has been shown to be membrane damage, and arylamide foldamers can cause rapid disruption of the outer membrane and also low-level changes to the inner membrane of E. coli. Increased permeability to small ions was observed in the inner membrane, resulting in protein translocation defects and thereby contributing to the activity. The membrane permeabilization action of arylamides is less extensive than that of natural antimicrobial peptides, which is likely to be associated with a lower risk of inflammatory responses.
Optimization resulted in a lead compound brilacidin (compound 4, PMX-30063; Fig. 8), which is a short arylamide sequence stabilized by intramolecular hydrogen bonds and substituted by small cationic and hydrophobic groups. In phase 2 clinical trials for the treatment of bacterial skin infections caused by drug-resistant S. aureus, brilacidin demonstrated good efficacy comparable with that of the currently used daptomycin (ClinicalTrials.gov, NCT01211470). Brilacidin dose-dependently depolarizes the S. aureus membrane and induces major stress regulons involved in cell wall and membrane stress.
Smith Thesis/COVID Trial Support Early Viral Brilacidin Use
[Last 3 sentences page 35] Brilacidin showed the greatest level of inhibition with direct viral treatment alone or in conjunction with the pre and post treatment. The data from the direct viral treatment indicates Brilacidin in [is] most effective in the early steps [stages] of viral replication. Brilacidin is a strong anti-viral candidate to be further developed and explored as a therapeutic against VEEV.
If a patient started study treatment within fewer than 7 days of onset of COVID-19 symptoms, patients in the Brilacidin 5-dose group achieved sustained recovery more quickly compared to the pooled placebo group (p=0.03). For this patient population, early treatment with Brilacidin from onset of symptoms appeared to have a potential positive impact on time to sustained recovery (the study’s primary endpoint), suggesting cases that can be treated close to initial onset of disease may be an attractive population to target for Brilacidin treatment.
Brilacidin Might First See Commercial Success As SYNERGIZER
An alternative approach to the development of novel antifungal drugs is the repositioning or repurposing of existing drugs. This approach is particularly promising because usually it identifies drugs that can synergize or enhance the activity of current antifungal agents and in many cases overcome developed resistance to a certain class of antifungals. Here, we have screened four repurposing libraries and identified enhancers and synergizers of CAS activity. We concentrated our attention on one of these synergizers, BRI, that is able to synergize not only with CAS but also VOR. To our knowledge, only two CAS synergizers have been previously identified against A. fumigatus, diphenyl diselenide and clofazimine75,76, and there are no previous reports showing BRI as a potential antifungal agent and synergizer of current antifungal drugs.
USP researchers have also shown Brilacidin to be synergistic with caspofungin in different types of fungi. Additive effects were similarly observed in Brilacidin combinations with voriconazole and geldanamycin against A. fumigatus, as well as with posaconazole against Mucorales. Separate in vitro laboratory testing evaluating Brilacidin in combination with other conventional antifungals – including caspofungin, fluconazole, posaconazole, amphotericin B and micafungin – demonstrated additive or synergistic inhibition of fungal growth.
In cell culture, in Aspergillus fumigatus (A. fumigatus), Brilacidin converted CAS from a fungistatic into a fungicidal drug, enabling it to overcome both drug resistance and biofilm formation. Brilacidin exerted, to a lesser degree, synergistic effects with VOR in A. fumigatus. Further in vitro testing showed Brilacidin synergized with CAS in C. albicans, C. auris and C. neoformans. In an A. fumigatus immunosuppressed mouse model in invasive pulmonary aspergillosis, Brilacidin plus CAS cleared infection in the lungs by almost 95 percent, compared to ~50 percent when each compound was administered individually. Brilacidin also showed in vitro an additive inhibitory effect when combined with POSA in several species of Mucorales, the main etiological agents of mucormycosis, commonly referred to as black fungus. Mortality rates can be as high as 90 percent in this fungal disease.
Due to the reduced number of available antifungal agents and the increased emergence of antifungal resistance in the clinical environment, there is an urgent need for novel antifungal drugs. There are few new potential antifungal drugs at different stages of clinical development,
Great article! The Impatient Should Also Take Note
Although there are still steps to be completed before the application can be performed in patients on a large scale, such results inspire the researchers to continue investigating the uses of brilacidin in various models to combat other species of fungi. “The process is long, but it is important to put the name of Brazil on the science map, to show that we, from universities in the Northeast, can contribute with value to research and publish articles in high impact journals such as those of the Nature group,” reinforces the professor.
IMO, the "long" process equates to a "long" opportunity for share acquisition.
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What does Merck think of this? https://ufrn.br/en/press/features-and-knowledge/69808/nova-arma-contra-os-fungos "One of the problems with treating mycoses is that there are basically only three groups of drugs used to treat serious diseases. The first and possibly best known by the population is the group named “azol”, a suffix present in many ointments and medicines that fight infections of this nature. The issue that hinders their effectiveness is that, because it is used in similar compounds to treat plant diseases, especially in agriculture, the patient can be infected by a resistant fungus that was selected in the environment when it came into contact with these fungicides. The second is amphotericin B, a drug available only in hospitals and that presents a high level of toxicity to the patient’s kidneys, which limits its use. The third is the echinocandins, a drug represented by caspofungin – present in the study -, whose disadvantage is concentrated in the fact that the drug does not kill the fungus, but only prevents its growth. Because the fungus mainly infects people with weakened bodies, the patient’s immune system is not always able to fully act and eliminate it, so it can occasionally regrow. The results noted in the paper indicate that combinations of BRI and clinically used antifungal drugs, such as caspofungin, improve the outcome of the treatment of aspergillosis and other fungal infections. “It can’t kill the fungus alone in vitro, but when I put it together with caspofungin, it potentiates its effect; with brilacidin, it kills the fungus. From the treatment point of view, this is very interesting,” explains Rafael Bastos.
The study has also tested the drug alone and in combination with caspofungin in mice and proved that, in vivo, it acts against the fungus both when administered alone and together with other drugs. This happens against infection in the lungs (pulmonary aspergillosis) as well as in the eyes (fungal keratitis).
In addition to Aspergillus fumigatus, brilacidin alone or in combination with caspofungin kills Cryptococcus (causing cryptococcosis), Candida albicans (causing candidiasis) and even the recently discovered super fungus, Candida auris. Cryptococcus is a fungus that is naturally resistant to caspofungin, but when it faces it together with brilacidin, it becomes sensitive."
CDC Discusses Candida auris: Doing Nothing or Not Enough
Danielle A. Rankin, PhD, MPH: If we do nothing, it's likely C auris will continue to spread throughout our health care facilities and may become endemic, allowing C auris to become an even greater risk to our patient populations. And in addition, we could also see the increasing level of resistance among C auris isolates.
Megan Lyman, MD: Just on resistance, only 3 main antifungal drug classes can be used for invasive Candida infections, including C auris. There was also an increase in a Candida-resistant cases that we've detected and [had] evidence of transmission, which is particularly concerning because it is our first line therapy for invasive Candida infections, including C auris.
ICT: What other pathogens lurking in the background that we need to worry about?
ML: There are many fungal pathogens; it's a whole kingdom. There are many changes, and we have seen more emerging fungal pathogens increasing resistance; C auris is a great example. We're continuing to monitor that. But there are some things going on, including climate change that may be selecting for some of these emerging pathogens to start popping up now. And things like antifungal and antimicrobial use are increasing and changing, and that's selecting for more resistant, emerging pathogens.
Leo has proven adept at acquiring the necessary funds when needed. It doesn't take much money to keep the lights on and that's all he has to do until times get better.
Personally, I'm happy to hear Leo's not taking calls. He's probably not at liberty to disclose very much anyway..
As far as I'm concerned, the more doubts about Leo and the long term viability of IPIX...the better.
Message in reply to: Yes all fine a well, but Ipix does not have money left to dilly dally and wait for a couple more years for any kind of success! That’s the elephant in the room
After the late-stage failures of the oral mucositis drugs of Oragenics, Soligenix and Galera, IMO, no company is going to be willing to RISK the many million$ it would take to finance a B-OM/P-3. IPIX has no funds for clinical trials and B-OM will just have to rest on the backburner until they do.
The licensing agreement with Alfasigma " to develop and commercialize locally-administered Brilacidin (e.g., foam, enema, gel), on a worldwide basis, for the treatment of Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS)" shows no signs of providing any significant financial gain to IPIX any time soon. This agreement was signed 4 years ago come July 2023.
NIH/NIAID and their proxies, as well as foreign entities, are investigating the scope of brilacidin's antiviral/antifungal capabilities and synergism with other drugs. IMO, it will probably be a year or two before any clinical trial(s) is announced in any of these areas. Candida Auris, while present in more than half of the 50 U.S. states, IMO, is not yet a big enough problem to warrant emergency action allowing for brilacidin to be used in combination with another drug based on invitro testing only. This, however, could rapidly change.
In January 2023, BeaMed signed a MULTIYEAR DEVELOPMENT AND SUPPORT AGREEMENT with Shina Systems, LTD. This suggest that, despite the possibility for quick FDA approval, BeaMed's next-generation laser based platform for epilepsy and cancer surgery is still a year or two away from market introduction.
IMO, BeaMed excluded, IPIX is not in the right position to be sold or partnered. I think a potential partner or buyer would see too much risk and would probably think there are better places to invest their capital. Additionally, I believe Leo has probably already fielded and rejected low-ball offers for indications or the company and, IMO, he has been very selective about the deals he makes.
Personally, I am heartened by all of this because I believe Leo will, ultimately, be successful in negotiating this long and winding road to success. I am also heartened by the negativity toward Leo and this stock in that I believe it has a depressing effect on IPIX's stock price, allowing me to continue to accumulate at these fire sale prices.
Yes, this is not a stock for the impatient, but for those who see what I see, it is a stock for the opportunistic.
Fungi, the Newest Emerging Microbe Threat Worldwide
Editor’s Note (3/21/23): The dangerous fungus Candida auris is spreading rapidly in hospitals and other health care facilities, the Centers for Disease Control and Prevention warned on Monday. Our June 2021 feature story, republished here, explains why C. auris can be so lethal and who is most at risk. It also describes why this pathogen and other deadly fungi are spreading throughout the world.
"75,000 people in the U.S. are hospitalized by fungi every year. 8.9 million are seen as outpatients"
Chiller [branch chief at the U.S. Centers for Disease Control and Prevention] knew all about C. auris—possibly more about it than anyone else in the U.S. Almost exactly four years earlier [2017] he and the CDC had sent an urgent bulletin to hospitals, telling them to be on the lookout. The fungus had not yet appeared in the U.S., but Chiller had been chatting with peers in other countries and had heard what happened when the microbe invaded their health-care systems. It resisted treatment by most of the few drugs that could be used against it. It thrived on cold hard surfaces and laughed at cleaning chemicals; some hospitals where it landed had to rip out equipment and walls to defeat it. It caused fast-spreading outbreaks and killed up to two thirds of the people who contracted it.
How fungi are becoming supercharged by climate change
Global warming could spark ‘unpredictable’ changes in fungi, making it more deadly, research shows. Rising temperatures may cause fungi to be more dangerous to our health, a new study reveals...
Pathogenic fungi are fungi that cause disease in humans and other organisms. Among the approximately 300 fungi known to be pathogenic to humans, Candida, Aspergillus and Cryptococcus are some of the most well known. They are currently most dangerous to immunocompromised people who lack the defences to prevent their spread...
Rising global temperatures are predicted to increase fungal diseases in humans, but they could also make those diseases more serious.
Studying the impact of heat stress on fungi, researchers found that higher temperatures led to rapid genetic changes in the human fungal pathogen Cryptococcus.
Higher temperatures were found to stimulate the fungus’s transposable ‘jumping genes’, accelerating the number of mutations and leading to adaptations in the way the genes are used and regulated...
This could lead to higher heat resistance, drug resistance and disease-causing potential, according to the research published in the science journal PNAS.
“This is a fascinating study, which shows how increasing global temperature may affect the fungal evolution in unpredictable directions… One more thing to worry about with global warming,” says Dr Arturo Casadevall, chair of molecular microbiology and immunology at Johns Hopkins University...
Fungal infections are already deadly, killing around 1.7 million people per year - and they're a "growing health threat", according to the World Health Organization (WHO). They are also becoming increasingly resistant to antifungal drugs used to treat them - and we currently lack alternatives.
Four fungi are placed in the 'critical priority group', including pathenogenic yeasts Cryptococcus neoformans, Candida auris and Candida albicans, along with Aspergillus fumigatus, a common mould found in soil.
Scientists Fear ‘Catastrophic’ COVID Combination With Another Virus
The SARS-CoV-2 virus is highly contagious but the current dominant strains are not very lethal. Its much rarer cousin in the betacoronavirus family of pathogens, MERS-CoV, is highly lethal but not very contagious. Now imagine a blend of the two—a respiratory virus with the most dangerous qualities of both. Contagious and lethal.
Basilea immediately came to mind after reading 'Frenchbroad's' comment. IMO, we shouldn't press her for her sources because confidentiality is essential to keeping the info pipeline open.
I think if you follow the link to their website, you will find that Basilea would be an excellent fit for IPIX. Here's why:
Basilea is a revenue-generating, commercial-stage Swiss biopharmaceutical company. Our activities are focused in the areas of hospital antibiotics and hospital antifungals. Our portfolio comprises of two marketed anti-infective brands (Cresemba® and Zevtera®) and several preclinical anti-infective assets. We are building on our potential for sustainable growth and valuation generation, based on increasing revenues and selective investments into internal and external innovation. Basilea was founded in 2000 and is located in the life sciences hub of the Basel area. Basilea has about 150 employees. Since 2004, Basilea is listed on the SIX Swiss Stock Exchange with the ticker symbol BSLN.
Don't forget IPIX can license B indications in the bacterial area and fungal area and still have the lucrative virus area for themselves or to further partner.
Basilea and IPIX have one thing in common. They both moved away from oncology.
We don’t currently have any vaccines for fungal infections, and as my colleague Keren Landman writes, “it’s not for lack of trying.” But the researchers working on preventive measures say that the rapid spread of Candida auris adds urgency to the mission for a drug-resistant fungal vaccine moonshot.
“There needs to be a vaccine. And it needs to be supported right now,” said Karen Norris, an immunologist at the University of Georgia’s veterinary school, who leads a team developing a potential fungal vaccine.
With the support of the National Institutes of Health, her team is designing a fungal vaccine to be cross-protective against several different fungal pathogens, potentially including Candida auris. They demonstrated in a paper published last year that the vaccine will induce an immune response in animals and particularly those that are immunosuppressed or immunocompromised.
They have yet to test it on humans. A phase one clinical trial would still be more than a year away, and that’s assuming they have the funding to undertake it.
“We are looking at the process for scaling up the manufacturing of this vaccine for development and for safety studies down the road in people,” Norris said. “We are hoping to partner [with the private sector] to advance this at a more rapid pace than where we are right now.”
NIH should not be confused with NIAID. NIAID is one of the 27 institutes and centers that make up the National Institutes of Health. There is probably more than one institute involved in fungal research, but the above research, IMO, doesn't involve NIAID because of the above-mentioned P-1 funding problems. NIAID develops designated drugs through P-2.
A successful phase 1 is not the end to FDA required safety data. The FDA requires safety data at all stages of drug development and even after the drug is on the market.
The criticisms of all the brilacidin testing reveals a lack of understanding of the drug approval process. Prior to drug approval, the FDA requires reams of all kinds of data.
The turning point for brilacidin will be when NIAID announces a phase1.
Innovation Pharmaceuticals enters research collaboration with USP
02/23/23 - IPIX The Company and University of Sao Paulo, Brazil, have entered into a collaborative research agreement to investigate the broad-spectrum activity and treatment potential of Brilacidin in fungal diseases. Under terms of the agreement, USP researchers are to conduct pre-clinical efficacy, mechanism, resistance and immunological studies of Brilacidin against Aspergillosis, Cryptococcus and Candida.Separate in vitro testing of Brilacidin's antifungal properties is underway by NIH/NIAID-affiliated researchers, with potential to bridge into in vivo models, formulation development support and clinical testing.
Innovation Pharmaceuticals announces new antifungal testing of Brilacidin
03/15/23 - IPIX Innovation Pharmaceuticals announced that based on positive findings new testing of Brilacidin in additional in vitro and in vivo models against hard-to-treat fungal pathogens is planned by NIH/NIAID-affiliated and other academic researchers. Brilacidin is the Company's defensin mimetic drug candidate exhibiting antimicrobial and immunomodulatory properties. Extensive in vitro testing of Brilacidin by these research groups against multiple pathogenic human fungi has been completed. Comparable to findings observed in testing by scientists at the University of Sao Paulo, Brazil, Brilacidin showed potent stand-alone inhibition in multiple isolates of C. neoformans, for which few effective treatments exist. Brilacidin showed promising stand-alone inhibition as well in multiple isolates of Mucorales, Fusarium sp., C. glabrata, C. parapsilosis, C. guillermondii, Lomentospora prolificans, Scedosporium apiospermum, Blastomyces dermatitidis and Histoplasma capsulatum. USP researchers have also shown Brilacidin to be synergistic with caspofungin in different types of fungi. Additive effects were similarly observed in Brilacidin combinations with voriconazole and geldanamycin against A. fumigatus, as well as with posaconazole against Mucorales. Separate in vitro laboratory testing evaluating Brilacidin in combination with other conventional antifungals - including caspofungin, fluconazole, posaconazole, amphotericin B and micafungin - demonstrated additive or synergistic inhibition of fungal growth. In related news, Brilacidin antifungal data was accepted for a scientific poster presentation at the 16th Annual European Conference on Fungal Genetics, held in Innsbruck, Austria, March 5-8, 2023, based on research conducted at USP and other academic institutions.
Until NIAID and/or USP announce they will be starting clinical trials there is basically nothing to see here. Important to remember that NIAID will take a drug through P-2, not out of the goodness in their hearts, but because if the drug is ultimately approved they intend to BUY and stockpile the drug for the U.S. government. This suggest the CASH will roll in quickly for a NIAID approved drug.
IMO, the cash will first roll-in from BeaMed. Hopefully, by the time NIAID has successfully advanced brilacidn through P-2, IPIX will have enough cash on hand to either complete a P-3 or negotiate a partnership from a position of financial strength.
I suspect NIAID is already looking into B/C. Auris
I assume NIAID learned, through the 2022 Brazilian study that:
In pre-clinical studies, Brilacidin shown to synergize with marketed antifungals against pathogenic species of aspergillosis, candidiasis, cryptococcosis and mucormycosis, and further exhibited potent stand-alone efficacy against Cryptococcus neoformans
There were at least 2,377 confirmed cases in the U.S. in 2022, according to CDC statistics. That total was a steep jump from the 1,474 cases in 2021 and continued a rapid increase from 2020, when there were just 757 confirmed cases.
Health officials said that the fungus’s resistance to antifungal medication is “particularly concerning” because those medications are often the first option for treatment, saying it necessitates research into better protection and prevention measures against the fungus.
“The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris,” a research paper into the spread of the fungus in the Annals of Internal Medicine said. “These findings highlight the need for improved detection and infection control practices to prevent spread of C auris.”
I think it's reasonable to assume that NIAID is aware of the Brazilian research and CDC data showing "dramatic increases" in c. auris and Bs possibilities relative to same. I think it's a good bet NIAID is already on this.
Message in reply to: CDC page regarding Candidia auris
If NIAID, as a result of their testing, deems brilacidin worthy, they will develop brilacidin through phase 2 for viral and/or fungal indications. Consider the following:
In which phase of clinical trials do the most pharmaceuticals fail?
Phase II clinical studies represent a critical point in determining drug costs, and phase II is a poor predictor of drug success: >30% of drugs entering phase II studies fail to progress, and >58% of drugs go on to fail in phase III.
Why would any BP want to assume these risks and costs when they can possibly make a deal later, after the gov't has assumed these risks and costs? This is just basic business sense.
For the most part, NIAID is driving this "brilacidin train" and, COVID aside, they haven't conducted any clinical trials yet.
CDC warns ‘dramatic-increase’ in deadly fungus across US
Candida aurism, a rare and sometimes deadly fungal disease, is spreading through the U.S., the Centers for Disease Control and Prevention (CDC) warned this week, citing a “dramatic” increase in cases.
The fungus, which affects primarily old people and those with weakened immune systems, rejects treatments from traditional antifungal medications and has a mortality rate of up to 60 percent, health officials said.
There were at least 2,377 confirmed cases in the U.S. in 2022, according to CDC statistics. That total was a steep jump from the 1,474 cases in 2021 and continued a rapid increase from 2020, when there were just 757 confirmed cases.
Health officials said that the fungus’s resistance to antifungal medication is “particularly concerning”because those medications are often the first option for treatment, saying it necessitates research into better protection and prevention measures against the fungus.
“The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris,” a research paper into the spread of the fungus in the Annals of Internal Medicine said. “These findings highlight the need for improved detection and infection control practices to prevent spread of C auris.”
The disease has now been tracked in half of the states in the U.S., and CDC officials said it was likely that the coronavirus pandemic worsened the spread of the fungus, as the increased attention on the COVID-19 virus meant there was less emphasis on screening for C. auris.
The virus was first reported in Japan in 2009, but researchers have tracked the earliest strain to South Korea in 1996. The fungus does not usually present a risk to young people.
It was not logic. It was a judgement (based on logic) and, considering the variables of the case of K-OC, one I stand by. I don't see the business sense in BP spending, perhaps, millions to buy K-OC and hundreds of millions more to develop a drug that as yet only has shown promise in the lab and a P-2 clinical trial comprised of 2 participants.
This is a unique case where the factors, IMO, suggest BP has better places to put its money. Again, I stand by that and I hope I'm wrong.
Message in reply to: By your logic no BP would never license anything for ovarian cancer from smaller companies?
A quick search for "ovarian cancer preclinical license agreement" found this update of a deal between Merck and Agenus from Nov 2020: An Agenus-discovered first-in-class ILT4 antibody, MK-4830, enters Phase 2
A $10 mio milestone payment for entering phase 2. Plus Agenus is eligible for up to an additional $85 million in milestones plus royalties on sales. Of course, the deal itself certainly brought in a couple of millions.
Sure, Ipix could never develop Kevetrin alone. But license it to BP at this stage is everyday-business and far from being a pipe dream.
Your find validates Leo's decision to back-burner Kevetrin
Kevetrin: Kevetrin (thioureidobutyronitrile) is a small molecule that induces cell cycle arrest and apoptosis in cancer cells through a multi-pronged mechanism that includes the activation and stabilization of p53. Kevetrin inhibited tumor growth and lengthened survival time in ovarian cancer mouse models . A recent phase II clinical trial (NCT03042702) showed stable disease in ovarian cancer patients , but with only two enrolled patients; these results require replication if Kevetrin is to progress as an ovarian cancer treatment.
Replication will require tens of millions of dollars that IPIX simply don't have. Further consider that:
In this analysis of US Securities and Exchange Commission filings for 10 cancer drugs, the median cost of developing a single cancer drug was $648.0 million. The median revenue after approval for such a drug was $1658.4 million.
11. The Future of p53-Based Therapies for HGSOC (High Grade Serious Ovarian Cancer)
The future remains bright for p53-based therapies for the treatment of HGSOC, given the high percentage of p53 mutations. However, there are several obstacles that need to be overcome for this class of therapeutics to be successful. Due to the abundance of heterogeneity associated with HGSOC, it is likely that one single therapy will not suffice for all patients. Therefore, treatment outcomes will depend on a variety of factors including, but not limited to, the following: specific p53 mutation status, BRCA 1/2 status, resistance to chemotherapy agents and/or PARP inhibitors, biomarkers, tumor origin site, stage, and Ad5-neutralizing antibody immunity status. Clinical therapies may need to be tailored based on a comprehensive analysis of these factors. Further research is desperately needed in this field to gain a greater understanding of ovarian cancer, including where it originates, how it spreads, and what biomarkers could be utilized for early detection.
IMO, a 2-person trial showing trial showing efficacy is probably not enough to attract suitors interested in ultimately spending hundreds of millions of dollars on K-OC. A potential suitor would also have to consider the 5 other p53 competing therapies (see article) in development as well as the many things we (science) don't fully understand about Ovarian cancer.
I would go as far to say that even if IPIX had the hundreds of millions of dollars to invest, given the many areas of "B" FREE research being conducted by gov'ts and educational institutions, to fully develop K-OC...it wouldn't be a wise investment.
Because many cancers have p53 problems, Kevetrin might have a future in cancer as a combo-therapy and I suspect we won't find out until after K's patent expiration in 2030 for the already stated reasons
Message in reply to: https://www.mdpi.com/2218-273X/13/1/159 This was published in January 2023. Does the company still own Kevetrin......Leo has never provided us with that answer. I have messaged him on this a few times with no response.
Fungal infections are becoming more common - NBC News
In the U.S., fungal infections are responsible for more than 75,000 hospitalizations and nearly 9 million outpatient visits each year, according to the Centers for Disease Control and Prevention. In 2021, around 7,200 people died from fungal diseases. These numbers, the CDC said, are likely an underestimate.
Australian Researchers Find Protein That Blocks COVID Infection
Australian scientists announced Friday they've discovered a protein in the lung that sticks to the COVID-19 virus like Velcro and forms a natural protective barrier in a person's body to block infection.
If your question "Does anyone know anything about this" is referring to the Novavax clinical trial, your article states that "Initial results are expected in Q1 2023."
Message in reply to: Does anyone know anything about this????
Farrell90, I see when someone hand you the ball you really run with it.
Great additional find on Subhash Dhawan's resume. It's an impressive one for sure.
She first filed a provisional patent on July 28, 2021 and I would bet the family farm that she retired, from the gov't, prior to that date because:
Under the law, federal employees who are inventors are entitled to a share of revenues that the government may obtain from licenses and royalties (not to exceed $150,000 per year per inventor).
I think IPIX's press release on September 15, 2020:
Laboratory Testing of Brilacidin for COVID-19 in Combination with Remdesivir Reduces Viral Load by Nearly 100 Percent
Could this invention flow from NIH's Brilicidin work?
NIH has an office in Gaithersburg, Maryland and the "swab" inventor, Subhash Dhawan, is also from Gaithersburg. Thus, it seems reasonable to assume she is a government scientist, who has been involved with brilicidin research or, at the very least, she's aware of the brilicidin research.
I also wonder if she came up with this "swab" idea after seeing the high-efficacy of the brilicidin/remdesivir combo?
In terms of a Sars-Cov2 prophylactic, the evidence suggest that her "swab" should have brilicidin on one end and remdesivir on the other.
There is also the possibility of different types of "swabs" for different types of viral afflictions.
This could be a "godsend" for China, Third World and even more advanced countries.
Yes, there is a chance Leo sells...but there's also a chance he won't. Leo would have to weigh the amount being offered for Kevetrin against many variables like the market size of TB.
The global tuberculosis drugs market was valued at US$ 1,755.29 million in 2021 and is estimated to reach US$ 2,407.35 million by 2029, growing at a CAGR of 9.68% during the forecast period (2022-2029).
Tuberculosis (TB), known as poor man’s disease, is caused by mycobacterium tuberculosis germs spread from person to person through the air. Tuberculosis drugs are also used post surgeries of the stent, bypass surgery, and others. TB usually affects the lungs and other parts of the body, such as the brain, the kidneys, or the spine. Across the globe, almost two billion people are infected with M. tuberculosis.
A major point that shouldn't be missed is that the laboratory evidence suggest Kevetrin could work as a standalone treatment for TB.
DDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride.
https://pubmed.ncbi.nlm.nih.gov/36719870/ Another variable is the identity of the payer and in Asia and Africa the payers are likely to be governments or agencies of the WHO, which should take care of distribution.
With Brilicidin/Kevetrin showing laboratory efficacy in the areas viruses, fungi and now TB, who knows, Leo might decide to go the way of Basilea.
The Power of Patience: (As well as hindsight)
Aug.15, 1985 - Apple (AAPL) - closing price $.05 ($1,000 = 20K shares I wish I had bought) Jun 16, 1987- Stock splits 2-1 - (I would have had 40K shares) Jun 21, 2000 - Stock splits 2-1 - (I would have had 80K shares) Feb 28, 2005- Stock splits 2-1 - (I would have had 160Kshares) Jun 19, 2014- Stock splits 7-1 - (I would have had 1.120M shs) Aug 28, 2014- Stock splits 4-1- (I would have had 4.48M shs)
Bottom Line: A $1,000 investment in Apple in 1985 would...as of Feb 1, 2023 (appl closing price $145) would be worth $650 MILLION (that I obviously don't have).
Patience is key with IPIX as well. I believe time will ultimately show that IPIX's anti-infective indications (viruses, fungi & TB) will be very lucrative. Maybe even more lucrative than Apple's i-pods, air pods, i-phones, etc.
In 2018, 1.7 billion people were infected by TB bacteria — roughly 23% of the world’s population. TB is the leading infectious disease killer in the world, claiming 1.5 million lives each year.
Of the 10 million individuals who became ill with TB in 2018, approximately three million were “missed” by health systems and do not get the care they need, allowing the disease to continue to be transmitted.
Here is the full research document. I add the underline. *The CFU by spread plate method showed in DDP combined with p53 promoter (Kevetrin hydrochloride) group decreased significately compared with DDP group (p<0.0001), while the number of colonies in DDP combined with p53 inhibitor (Pifithrin -a hydrobromide) group increased greatly compared with DDP group (p<0.0001) (Fig 4C). Moreover, the bacterial number in cells could also be significantly reduced by using Kevetrin hydrochloride alone, and this effect was positively correlated with the concentration of the p53 promoter (Fig 4D). Compared with RIF, RIF combined with Kevetrin hydrochloride had a stronger effect on the elimination of intracellular mycobacteria (Fig 4E).*
What is ‘super gonorrhea’? Researchers identify new case
The term “super gonorrhea,” according to the World Health Organization (WHO), refers to strains of gonorrhea that have “high-level resistance” to current antibiotic treatments. Officials with WHO say these resistant strains can develop and spread thanks to genetic mutations in the bacteria N. gonorrhoeae, or through the overuse of antibiotics (or poor quality of antibiotics used in treatment), among other factors.
Both WHO and the U.S. Centers for Disease Control and Prevention (CDC) further noted that gonorrhea, in general, has become better at evading treatments over the years.
‘Concerning’ strain of gonorrhea detected in Massachusetts, officials say
JAN 19, 2023 BOSTON (WWLP) – A novel strain of antibiotic-resistant gonorrhea has been identified in Massachusetts, health officials announced Thursday.
The strain was found to resist five classes of antibiotics, a first in the U.S., according to the Massachusetts Dept. of Public Health (DPH).
"Gonorrhea has been increasing in Massachusetts and nationally, adding to concerns about the potential spread of this strain which is more difficult to treat.
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