BooDog
3 years ago
Diffusion Pharmaceuticals Doses First Patients in ILD-DLCO Trial
Diffusion Pharmaceuticals Inc.
Thu, December 16, 2021, 8:59 AM·5 min read
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Third of Three TSC Oxygenation Trials
CHARLOTTESVILLE, Va., Dec. 16, 2021 (GLOBE NEWSWIRE) -- Diffusion Pharmaceuticals Inc. (NASDAQ: DFFN) (“Diffusion” or the “Company”), a biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen to areas where it is needed most, today announced it has dosed the first patients in its ILD-DLCO Trial. The trial will evaluate the Company’s lead product candidate, trans sodium crocetinate (“TSC”), in patients with previously diagnosed interstitial lung disease (“ILD”).
“We designed the ILD-DLCO Trial to evaluate the effects of TSC on the enhancement of oxygen uptake through the lungs and into the bloodstream of ILD patients,” said Chris Galloway, M.D., Chief Medical Officer of Diffusion. “This is the third of our Oxygenation Trials designed to evaluate the effects of TSC on the continuum of oxygen transport from uptake to delivery, and ultimately end organ utilization. We believe these data will provide further supportive information regarding TSC’s novel mechanism of action and dose-response characteristics and support the broad potential of TSC to treat a variety of conditions complicated by hypoxia.”
The ILD-DLCO Trial is a double-blind, randomized, placebo-controlled study which will evaluate the effects of TSC on the diffusion of carbon monoxide through the lungs (“DLCO”) in patients with previously diagnosed interstitial lung disease who have a baseline DLCO test result that is abnormal. DLCO will act as a surrogate measure of oxygen transfer efficiency, or uptake, from the alveoli of the lungs through the plasma, and onto hemoglobin within red blood cells. Diffusion intends to enroll 27 patients with confirmed ILD who will be randomized in a 2:1 ratio to a single 2.5mg/kg dose of TSC or placebo via IV bolus. The study is statistically powered to evaluate the difference in effect of TSC versus placebo on improvement in DLCO measurements. In addition, patients will undergo a standard six-minute walk test intended to assess functional improvement in exercise capacity. Diffusion anticipates completing the trial in the first quarter of 2022, with topline results reported within two months of study completion.
While the Company intends to continue developing data to support TSC’s potential uses across a broad spectrum of indications complicated by hypoxia, it recently announced that its near-term focus will be the design and execution of a clinical program to support the use of intravenously administered TSC as an adjunctive treatment for hypoxic solid tumors, and that it intends to obtain input from the U.S. Food and Drug Administration on the program’s design in early 2022.
About Diffusion Pharmaceuticals Inc.
Diffusion Pharmaceuticals Inc. is a biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen to areas where it is needed most. Diffusion’s lead product candidate, TSC, is being developed to enhance the diffusion of oxygen to tissues with low oxygen levels, also known as hypoxia, a serious complication of many of medicine’s most intractable and difficult-to-treat conditions, including hypoxic solid tumors. In November 2021, based on the preclinical and clinical data accumulated to date and the significant unmet medical need, Diffusion announced that its near-term focus will be the design and execution of a clinical program to support the use of intravenously administered TSC as an adjunctive treatment for hypoxic solid tumors. For more information, please visit us at www.diffusionpharma.com.
Forward-Looking Statements
This press release includes express and implied forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding the Company’s near-term strategic priorities, anticipated timelines for the initiation, completion, and announcement of data from the Company’s Oxygenation Trials and Hypoxic Solid Tumor Program, the relevance and significance of any such data, and the potential therapeutic value of TSC. The Company may, in some cases, use terms such as “believes,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “approximately,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Although the Company believes that it has a reasonable basis for each forward-looking statement contained herein, forward-looking statements by their nature involve risks and uncertainties, known and unknown, many of which are beyond the Company’s control and, as a result, the Company’s actual results could differ materially from those expressed or implied in any forward-looking statement. Particular risk and uncertainties include, among other things, those related to: the Company’s ability to design, initiate, enroll, execute, and complete its planned studies evaluating TSC; the likelihood and timing of regulatory approval of TSC, if any, for the treatment of solid tumors complicated by hypoxia or any other indication, or the nature of any feedback the Company may receive from the U.S. Food and Drug Administration or other regulatory bodies; the impact of supply chain and other supplier issues on the Company’s clinical development program and associated timelines; the Company’s ability to protect and expand its intellectual property portfolio; the Company’s ability to maintain compliance with the continued listing standards of Nasdaq; general economic, political, business, industry, and market conditions, including the ongoing COVID-19 pandemic; and the other factors discussed under the heading “Risk Factors” in the Company’s filings most recent Annual Report on Form 10-K and other filings with the U.S. Securities and Exchange Commission. Any forward-looking statements in this press release speak only as of the date hereof (or such earlier date as may be identified) and, except as required by applicable law, rule, or regulation, the Company undertakes no obligation to update any such statements after the date hereof.
Contacts:
Tiberend Strategic Advisors, Inc.
Maureen McEnroe, CFA/ Lisa Sher
mmcenroe@tiberend.com/ lsher@tiberend.com
Media Contact:
Kate Barrette
RooneyPartners
Kbarrette@rooneypartners.com
BooDog
3 years ago
From USPTO...
https://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=11,185,523.PN.&OS=PN/11,185,523&RS=PN/11,185,523
Clearly this is not a small deal. Certainly need to do a bit more dd on this but also glad I stumbled on this little bio.
Edit: Yeah, I think someone found the patent before the company had a chance to release the PR. Just released on Nov 30, 2021 but I didn't see a time.
excerpt...
SUMMARY
In one embodiment, the disclosure includes a method of treating cancer (solid tumor) in a mammal (e.g. human) comprising a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, b) administering to the mammal radiation therapy, wherein said bipolar trans carotenoid salt is administered at time and at a dose causing increased partial pressure of oxygen in the tumor during administration of said radiation.
In a preferred embodiment, the bipolar trans carotenoid is TSC administered at a dose of 0.15-0.35 mg/kg 45-60 minutes prior to administration of said radiation therapy. In some embodiments, the subject mammal is also administered chemotherapy in addition to the radiation therapy, e.g. administering temozolomide 7 times per week for 6 weeks.
A still further embodiment of the disclosure relates to a method of treating cancer (solid tumor) in a mammal (e.g. human) comprising a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, b) administering chemotherapy to the mammal, wherein said bipolar trans carotenoid salt is administered at a time and at a dose causing increased partial pressure of oxygen in the tumor during administration of said chemotherapy.
In a preferred embodiment, TSC administered at a dose of 0.75-2.0 mg/kg 1-2 hour prior to administration of said chemotherapy.
The cancer is selected from the group consisting of squamous cell carcinomas, melanomas, lymphomas, sarcomas, sarcoids, osteosarcomas, skin cancer, breast cancer, head and neck cancer, gynecological cancer, urological and male genital cancer, bladder cancer, prostate cancer, bone cancer, cancers of the endocrine glands (e.g. pancreatic cancer), cancers of the alimentary canal, cancers of the major digestive glands/organs, CNS cancer, and lung cancer. The chemotherapy is selected from the group consisting of alkylating agents, antimetabolites, antitumor antibiotics, topoisomerase inhibitors, and anti-microtubule agents. In some embodiments, the subject mammal is also administered radiation therapy in addition to the chemotherapy.
In an advantageous embodiment, the bipolar trans carotenoid is TSC administered at a dose of 0.75-2.0 mg/kg, 1-2 hrs. prior to administration of said chemotherapy. The chemotherapy is one or more compounds selected from the group consisting of gemcitabine, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, nab-paclitaxel (albumin-bound paclitaxel), capecitabine, cisplatin, elotinib, paclitaxel, docetaxel, and irinotecan liposome.
In one embodiment, the method is administering 1.5 mg/kg TSC 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering gemcitabine as an IV infusion once per week for 3 weeks followed by a week of rest.
In another embodiment, 1.5 mg/kg TSC is administered 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering nab-paclitaxel as an IV infusion followed by gemcitabine as an IV infusion, once per week for 3 weeks followed by a week of rest.
In another embodiment, the subject disclosure relates to a method of treating a cancer of the pancreas in a mammal (e.g. human) comprising: a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, and b) administering to the mammal chemotherapy, wherein the bipolar trans carotenoid salt is administered at a time and at a dose causing increased partial pressure of oxygen in the tumor during administration of the chemotherapy.
In an advantageous embodiment, the bipolar trans carotenoid is TSC administered at a dose of 0.75-2.0 mg/kg, 1-2 hrs. prior to administration of said chemotherapy. The chemotherapy is one or more compounds selected from the group consisting of gemcitabine, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, nab-paclitaxel (albumin-bound paclitaxel), capecitabine, cisplatin, elotinib, paclitaxel, docetaxel, and irinotecan liposome.
In one embodiment, the method is administering 1.5 mg/kg TSC 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering gemcitabine as an IV infusion once per week for 3 weeks followed by a week of rest.
In another embodiment, 1.5 mg/kg TSC is administered 45-60 minutes prior administering the chemotherapy, and administering the chemotherapy is administering nab-paclitaxel as an IV infusion followed by gemcitabine as an IV infusion, once per week for 3 weeks followed by a week of rest.
The disclosure also relates to a method of treating a cancer of the brain (e.g. glioblastoma) in a mammal (e.g. human) comprising: a) administering to the mammal a bipolar trans carotenoid salt having the formula: YZ-TCRO-ZY where: Y=a cation which can be the same or different, Z=a polar group which can be the same or different and which is associated with the cation, and TCRO=a linear trans carotenoid skeleton with conjugated carbon-carbon double bonds and single bonds, and having pendant groups X, wherein the pendant groups X, which can be the same or different, are a linear or branched hydrocarbon group having 10 or less carbon atoms, or a halogen, and b) administering radiation therapy to the mammal wherein the bipolar trans carotenoid salt is administered at time and at a dose causing increased partial pressure of oxygen in the tumor during administration of said radiation.
When the bipolar trans carotenoid is TSC, it is administered at a dose of 0.15-0.35 mg/kg 45-60 minutes prior to said administration, typically external beam radiation therapy. In one embodiment, the radiation therapy is administering 5 times per week for 6 weeks. In another embodiment, the method includes administering chemotherapy to the mammal, e.g. administering temozolomide 7 times per week for 6 weeks.
In all of the above embodiments, advantageously the bipolar trans carotenoid salt is TSC is in the form of a composition with a cyclodextrin.
CrazyC
3 years ago
8-K just filed... An additional 180 day extension from the Nasdaq to meet the minimum bid price...
https://www.sec.gov/ix?doc=/Archives/edgar/data/1053691/000143774921025519/dffn20211105_8k.htm
Item 3.01 - Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing.
As previously disclosed, on May 6, 2021, Diffusion Pharmaceuticals Inc. (the “Company”) received a written notice (the “May Notice”) from the staff (the “Staff”) of the Listing Qualifications Department of The Nasdaq Stock Market, LLC (“Nasdaq”) relating to the minimum bid price requirement contained in Nasdaq Listing Rule 5550(a)(2) (the “Bid Price Rule”). The May Notice indicated that the Company was not in compliance with the Bid Price Rule because the bid price for the Company’s common stock had closed below $1.00 per share for the previous 30 consecutive business days. In accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Company was provided 180 calendar days, or until November 2, 2021, to regain compliance with the Bid Price Rule.
On November 3, 2021, the Company received an additional notice from the Staff (the “November Notice”) providing that, although the Company had not regained compliance with the Bid Price Rule by November 2, 2021, in accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Staff has determined that the Company is eligible for an additional 180 calendar days from the date of the November Notice, or until May 2, 2022, to regain compliance with the Bid Price Rule. To regain compliance, the bid price for the Company’s common stock must close at $1.00 per share or more for a minimum of 10 consecutive business days.
The November Notice has no effect on the listing or trading of the Company’s common stock at this time, and the Company is currently evaluating its alternatives to resolve this listing deficiency, including, if necessary and subject to the approval of its board of directors and stockholders, implementing a reverse stock split.
Spideyboy
3 years ago
Hi wgg2,
As requested, I just had a look at DFFN.
While I don't think there should be a problem with safety of the product, there otherwise is very little to go on to observe efficacy. Even at the highest level of 1.5mg/kg every 6 hours (0.25mg per hour on average), when we consider that this product is trying to increase essentially plasma permeability to oxygen molecules by 'organising water molecules' then there is an awful lot of water molecules in the cardiovascular system. I don't see how that amount of drug related to amount of water will have much of an effect. Not only that but the idea is to enhance the oxygen permeability close to hypoxic tissues, so that means that logically a very very small amount of the molecule will be present in the vasculature at the specific hypoxic tissue site, which I assume would further reduce the efficacy for that tissue.
The covid trial was not only small at 24 patients, but then, that itself was divided up into 4 cohorts. So I assume 6 in each. And no control. I don't really see the ability to come to any conclusions there. Essentially while the drug will probably do what it is designed for, it's not particularly complicated, just using a large hydrophobic chain, I would feel the dosage will likely need to be increased considerably to observe a therapeutic effect. I could be wrong though as in the limited pre-clin data in the company presentation, they apparently observed statistically significant effect in rats at 0.02mg/kg every 10 mins for 60 mins (0.12mg per hour average). So far we have seen, the human dosage of 1.5mg/kg, which is on an average bases 2x greater, was apparently starting to see a benefit.
Also thus far I don't see any information on half-life or clearance, so difficult to understand how much stays in the system for how long, which would of course have important impact on efficacy.
Additionally a quick google search found these 2 papers,
1 of them on dogs, found that a dose of 0.1mg/kg had no effect in hypoxia.
No effect of trans sodium crocetinate on maximal O(2) conductance or V(O(2),max) in moderate hypoxia
https://pubmed.ncbi.nlm.nih.gov/12660103/
Then in this human study in PAD, they present it in a positive light, but the sample again is low and sub-divided into even smaller samples. So I don't feel it is reliable. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182020/
That's all I can say for now.
It will be very important to see efficacy from decent sized cohorts before being able to be clear to see any signal. And again dosage I feel will need to be considerably higher. I don't know how high the dosage will be allowed to go.
Best,
Spidey
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