Cobus Loots, CEO of Pan African Resources, on delivering sector-leading returns for shareholders. Watch the video here.
A Phase I trial of approximately 20 patients will be conducted at the Medical College of Wisconsin (MCW) to evaluate the safety and efficacy of Gallium Maltolate (GaM) in the treatment of Glioblastoma Multiforme (GBM). The trial, funded by IQ-AI, Ltd., was developed in part based on the results of a preclinical study led by medical oncologist Christopher Chitambar, MD, Emeritus Professor of Medicine and Biophysics, Division of Hematology and Oncology at MCW.
In the preclinical study, treatment with oral GaM caused a dramatic inhibition of tumor growth that was matched by a significant increase in overall survival. Dr. Christopher Chitambar’s group has shown that GaM kills cancer cells by “hijacking” iron metabolism. Essentially, the cancer cells are tricked into consuming GaM instead of iron, starving the tumor and ******ing cancer growth.
GaM is a metal-based compound with anticancer activity that can be administered orally. In prior FDA-approved Phase 1 clinical trials, oral GaM demonstrated low toxicity and was well tolerated. Lawrence R. Bernstein, PhD, is a co-investigator on the trial and will serve as the expert regarding the drug substance and formulations. He will also facilitate sourcing of the clinical-quality GaM. Dr. Chitambar and his colleague, Jennifer Connelly, MD, Associate Professor of Neurology, will be the co-principal investigators of the trial, which marks the first time an oral form of GaM will be used in GBM patients.
The neuro imaging platform of Imaging Biometrics, LLC (IB), a wholly owned subsidiary of IQAI, will be used to quantitively monitor tumor volumes. The FDA cleared IB Neuro™ and Delta T1™ maps have been used extensively in multi-center clinical trials to assess the efficacy for an array of brain tumor treatments.
If the outcomes look promising, IQAI will enlist a team of regulatory experts in attempt to accelerate the time to market, such as the Orphan Drug program, to benefit patients and their families. “We are taking this one step at a time and need to let the trial progress,” said Michael Schmainda, CEO of IB. “We are working with an excellent team of scientists and clinicians, and everyone is eager to move this study forward.”
GBM is the most common and aggressive primary brain cancer, with limited treatment options and a dismal prognosis. Current treatment involves maximal surgical resection followed by radiation therapy and chemotherapy (bevacizumab and temozolomide). The median survival of patients is only around 14 months. Despite decades of research, only incremental gains have been made to extend or enhance the quality of life.
https://www.appliedradiology.com/articles/phase-i-trial-to-evaluate-safety-efficacy-of-gallium-maltolate-for-glioblastoma-multiforme
Here’s the latest instalment in our news updates from Blackford Platform Partners.
Visualization and analytical solutions developer Imaging Biometrics highlighted a new paper in which IB Neuro, the company’s MR dynamic susceptibility contrast (DSC) perfusion platform, demonstrated clinical application throughout all phases of brain tumor management.
https://academic.oup.com/neurosurgeryopen/article/2/4/okab029/6370918
Neurosurgery Open, Volume 2, Issue 4, December 2021
ABSTRACT
BACKGROUND AND IMPORTANCE
Distinction of brain tumor progression from treatment effect on postcontrast magnetic resonance imaging (MRI) is an ongoing challenge in the management of brain tumor patients. A newly emerging MRI biomarker called fractional tumor burden (FTB) has demonstrated the ability to spatially distinguish high-grade brain tumor from treatment effect with important implications for surgical management and pathological diagnosis.
CLINICAL PRESENTATION
A 58-yr-old male with glioblastoma was treated with standard concurrent chemoradiotherapy (CRT) after initial resection. Throughout follow-up imaging, the distinction of tumor progression from treatment effect was of concern. The surgical report from a redo resection indicated recurrent glioblastoma, while the tissue sent for pathological diagnosis revealed no tumor. Presurgical FTB maps confirmed the spatial variation of tumor and treatment effect within the contrast-agent enhancing lesion. Unresected lesion, shown to be an active tumor on FTB, was the site of substantial tumor growth postresection.
CONCLUSION
This case report introduces the idea that a newly developed MRI biomarker, FTB, can provide information of tremendous benefit for surgical management, pathological diagnosis as well as subsequent treatment management decisions in high-grade glioma.
Iqai tweet!
https://twitter.com/IQAI_IB/status/1476300541735190535
Authors
Hisham S Alhajala 1 , John L Markley 2 , Jin Hae Kim 2 , Mona M Al-Gizawiy 3 , Kathleen M Schmainda 3 , John S Kuo 4 , Christopher R Chitambar
The cytotoxicity of gallium maltolate in glioblastoma cells is enhanced by metformin through combined action on mitochondrial complex 1
New drugs are needed for glioblastoma, an aggressive brain tumor with a dismal prognosis. We recently reported that gallium maltolate (GaM) ******s the growth of glioblastoma in a rat orthotopic brain tumor model by inhibiting mitochondrial function and iron-dependent ribonucleotide reductase (RR). However, GaM's mechanism of action at the mitochondrial level is not known. Given the interaction between gallium and iron metabolism, we hypothesized that gallium might target iron-sulfur (Fe-S) cluster-containing mitochondrial proteins. Using Extracellular Flux Analyzer technology, we confirmed that after a 24-h incubation, GaM 50 µmol/L inhibited glioblastoma cell growth by <10% but inhibited cellular oxygen consumption rate by 44% and abrogated mitochondrial reserve capacity. GaM blocked mitochondrial complex I activity and produced a 2.9-fold increase in cellular ROS. NMR spectroscopy revealed that gallium binds to IscU, the bacterial scaffold protein for Fe-S cluster assembly and stabilizes its folded state. Gallium inhibited the rate of in vitro cluster assembly catalyzed by bacterial cysteine desulfurase in a reaction mixture containing IscU, Fe (II), DTT, and L-cysteine. Metformin, a complex I inhibitor, enhanced GaM's inhibition of complex I, further increased cellular ROS levels, and synergistically enhanced GaM's cytotoxicity in glioblastoma cells in 2-D and 3-D cultures. Metformin did not affect GaM action on cellular iron uptake or transferrin receptor1 expression nor did it enhance the cytotoxicity of the RR inhibitor Didox. Our results show that GaM inhibits complex I by disrupting iron-sulfur cluster assembly and that its cytotoxicity can be synergistically enhanced by metformin through combined action on complex I.
https://pubmed.ncbi.nlm.nih.gov/32391122/
Just a few failed science experiments…lowest SP in 5 years….how long you going to give the company to come up with something the market wants ? It’s a massive failure, constant excuses , constant raises, it should be investigated really….
Still waiting for the Chinese payment…. Lol
Lol at least do a little bit of research before deramping you sad T. W. A. T
Lanstead “spontaneously”approached us(hopefully means they see value down here). Looking at their website it states
Generally, Lanstead’s minimum investment criteria are:
Invest in companies listed in LSE/AIM, European, ASX and TSX(Main) markets
Management must demonstrate how funds will drive growth
Maximum shareholding of 29.9%
Investments generally between £2 – £20 million
Strange that the amount is lower hopefully they will take advantage of the lower price.
Their team seems to know their ****
Nate Stander
Nate Stander has been with Lanstead for 8 years and is a Vice President and Senior Analyst. Nate has extensive experience in fundamental analysis and modeling. Prior to joining Lanstead, Nate worked as an Analyst in the Finance Division at Goldman Sachs and at PricewaterhouseCoopers on the Capital Markets Team. Nate holds a Bachelor of Accountancy from Brigham Young University Idaho.
Mark Holden
Mark Holden is a Co-Founder of Lanstead with more than 25 years of experience investing in and advising growth companies in the global financial markets. Mark previously founded and led one of the growth equity investment practices at JPMorgan Partners (“JPMP”), was a Principal with Trident II, L.P., and held several positions at Morgan Stanley & Co. in New York. He has also served as a director of a number of publicly quoted and private companies. Mark received a B.S., cum laude with University Honors from Brigham Young University and an M.B.A. from Harvard Business School.
Interesting remarks at the end of interview regarding breast and prostate cancer also AR extremely confidant both nxp004 and nxp002 will be a success. Perhaps they had to spill the beans on nxp004 to cement funding so a little slip at the end of the interview means everyone is now updated on it. Still very nice to have an institution on board
Guess it’s back to waiting!!
GLA !!
The net proceeds of the Sharing Agreements received by the Company will be used primarily to provide funding for:
o Further research and development activities on its main assets NXP002 and NXP004;
o Business development activities with potential licensees for both assets; and
o General working capital.
is now evaluating the durability of the therapy’s anti-fibrotic effects in these rats, with results expected by early 2022.
Earlier this year, Nuformix announced that it would be receiving a U.S. patent for NXP002 and its therapeutic use.
https://pulmonaryfibrosisnews.com/2021/11/29/nuformixs-nxp002-ipf-shows-promise-preclinical-studies/
pulmonary fibrosis news
Nuformix is focused on repurposing medications approved for one health condition — and proven to be safe for human use — to treat scarring-related conditions and cancer, thereby cutting both the costs and time required to develop a safe and effective treatment.
The company uses cocrystal technology to modify the chemical structure of approved compounds without altering their therapeutic potential.
Nuformix’s lead therapy candidate, NXP002, is a new formulation of tranilast, an oral antiallergic medication shown to have anti-scarring effects.
Studies conducted by the U.K.-based company also showed that tranilast reduces lung tissue scarring, or fibrosis, by suppressing the production of extracellular matrix (ECM) proteins. When present in excessive levels, they contribute to IPF. The ECM is the network of proteins and other molecules that surrounds and supports cells in tissues.
“Tranilast is poorly soluble, meaning it is not well absorbed into the body and tissues, and it also has issues regarding systemic toxicity,” Brindley said, adding that NXP002 “shows greater solubility than the original [compound], allowing it to be delivered to the lungs that are the site of action for IPF.”
By delivering NXP002 directly into the lungs, the company anticipates that “a lower dose will be required to produce a pharmacological and therapeutic effect with reduced systemic toxicity compared to oral dosing,” Brindley said.
Previous studies in lab-grown lung tissue collected from IPF patients showed that NXP002 reduced fibrosis and inflammation and that these effects were increased when the therapy was combined with standard IPF treatments — Genentech’s Esbriet (pirfenidone) and Boehringer Ingelheim’s Ofev (nintedanib).
Newly announced data concern additional research focused on the feasibility of inhaled delivery and its effects in rats.
First, researchers found that NXP002 could be formulated into a simple and stable solution with properties suitable for inhaled delivery through nebulization, which creates a fine mist of the medication. The new formulation was also able to achieve the right particle size range for lung delivery using off-the-shelf and commonly used nebulizer devices.
These findings supported the feasibility of delivering NXP002 through nebulization, which was then tested in rats. In these animal studies, researchers evaluated the therapy’s pharmacokinetics (movement into, through, and out of the body) and pharmacodynamics (effects on the body) when delivered through nebulization.
Results showed that NXP002 made its way efficiently to the animals’ lungs, achieving significant levels of exposure in that organ while limiting exposure to the rest of the body compared with oral dosing. In addition, inhaled delivery of NXP002 resulted in a dose-dependent reduction in the levels of fibrosis-relevant mediators.
As part of NXP002’s preclinical data package, the company is now evaluating the du
Nuformix plc
("Nuformix" or the "Company")
Positive pre-clinical data on NXP002
Nuformix plc (LSE: NFX), a pharmaceutical development company targeting unmet medical needs in fibrosis and oncology via drug repurposing, provides an update on its lead asset, NXP002, which it is currently developing as a potential novel treatment for Idiopathic Pulmonary Fibrosis ("IPF"). This update comes as a result of positive data received following initial pre-clinical studies.
NXP002 is a repurposed, new form of tranilast, that the Company is developing in an inhaled formulation for direct delivery to the lungs. Nuformix has successfully performed a number of pre-clinical studies as planned to generate a robust data package. The studies completed of the data package thus far comprise of:
- in vitro studies to demonstrate that NXP002 can be formulated in a formulation suitable for inhaled delivery by nebulisation; and
- in vivo studies to look at the pharmacokinetics and pharmacodynamics of NXP002 in a pre-clinical species when inhaled.
The in vitro studies demonstrated that it is feasible to formulate NXP002 into a simple and stable solution which has suitable properties for delivery via nebulisation. The data generated on these formulations also show that the drug can be efficiently delivered in the right particle size range for lung delivery using off-the-shelf and commonly used nebuliser devices. Thus, Nuformix believes that the delivery of NXP002 by nebulisation is feasible.
The first of the in vivo studies evaluated the pharmacokinetics of NXP002 when delivered by nebulisation to rats. This study demonstrated that NXP002 can be efficiently delivered to the lung, achieving significant drug levels, whilst limiting systemic exposure compared to oral dosing.
The second in vivo study evaluated the pharmacodynamics of NXP002 when delivered by nebulisation. This study showed that inhaled NXP002 could dose-dependently regulate the production of fibrosis-relevant mediators.
The final planned study as part of the NXP002 pre-clinical data package is an in vivo study investigating the durability of the pharmacodynamic effect. The Company anticipates receiving the data for this study in early 2022.
Dr Anne Brindley, CEO of Nuformix, said: "We're delighted with the positive readout of this data so far and it further cements our belief in NXP002 as a valuable asset. Tranilast is poorly soluble, meaning it is not well absorbed into the body and tissues, and it also has issues regarding systemic toxicity. NXP002 is a new form of tranilast that shows greater solubility than the original drug, allowing it to be delivered to the lungs that are the site of action for IPF. By delivering directly to the lungs, we anticipate that a lower dose will be required to produce a pharmacological and therapeutic effect with reduced systemic toxicity compared to oral dosing.
Unless they (the bod including jh/dg) have decided they’re happy with what we have and looking for the end game. Nxp001 hopefully keeps the lights on until the other 2 come to fruition?
Interested to see who/if we get a new CEO and what their plans are upon joining