Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Speculations and opinions are no evidence.
Repeating the same lies over and over don't make them facts.
And remember, your Occam sucks.
Great! From what I was reading in the update this is exactly what I was thinking would happen. RDGL knows what the FDA wants to see and how the data of the rabbit study will be used/assessed. I think they are very confident about the outcome of the study and don't feel a need for a meeting that would only delay the final submission further.
"That's just the way the program works."
Sounds like you have been involved in an EFS/IDE before. Could you let us know for which device?
I never claimed that the 3 and 6 week PET imaging was looking at Y90. It doesn't have the sensitivity at 6 weeks. I know better than that.
However there is Y90 PET imaging after application and (I assume) gelation, which I was referring to.
Here ye go again, "Dr. Fisher is/was a Y90 positron emission denier" and "FDA asked for additional animal testing at first meeting" with no evidence whatsoever. Remember, your Occam sucks!
For comparison, the FDA granted accelerated approval for adagrasib late last year.
Look at Table 7 for efficacy:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/216340s000lbl.pdf
Only 0.9 % Complete Response (CR) and 42% Partial Response (PR)
and with a slew of adverse reactions, many Grade 3-4 (Section 6).
Most likely RadioGel will have a much better profile.
Then they will ask him for hard evidence and he will have.... NONE!
Updated guidance for Therasphere:
https://pubmed.ncbi.nlm.nih.gov/36114872/
The authors include Beau Toskich, one of the Mayo physicians collaborating with RDGL. We are in good hands.
There is a lot of product info that has to go in an IDE (https://www.fda.gov/medical-devices/investigational-device-exemption-ide/ide-application). Just to draft the initial IDE must have taken months in 2021. Dr K is taking full advantage of the EFS program and the increased interactions with the FDA to ensure a successful final submission.
All should remember that Dr K has no prior experience in drug/device development. He is learning on the fly. I find it remarkable the amount of work he is able to accomplish on a relatively small budget. Contrary to the allegations of some, he has not wasted money.
And yes, I agree, some of the work could not have been done years ago. The design of the containment study appears to be guided in part by the interactions with the Mayo docs and they are treating it almost like a rehearsal of the clinical protocol. Even if it takes a little longer, it will be done in parallel with all the other activities so not much time we be lost.
The actual Jan 3rd update was different. It was edited later to reflect study initiation; I don't remember when the update happened. It may have been 2nd week of Jan.
One month does not move us to an another inning. This is nothing in the drug/device development time scale.
Since we supposedly past the 7th stretch we are at bottom of the 7th, not the top. Please don't put us back.
Based on the post below, there are still a lot things to wrap-up before IDE submission so there is time to complete the rabbit study. I prefer setting my expectations based on a realistic worst-case scenario of 3+3 weeks + 10 day, which brings us to end of Feb for study completion. Add one month for analysis and reporting (remember this is a GLP-like study) and RDGL could be ready to submit a report by end of Mar. The reporting could take longer but they can submit a draft, non-audited, report to the FDA when requesting the meeting to save time (I've done that before). The finalized report would then be included with the IDE submission.
“We are entering the final phase of validating our essential procedures. This process includes production to specification, sterility, shelf-life, and pre-mixing of our components. This data will be necessary to address critical sections of the subsequent IDE submittal.”
That's me. Trying to add few more shares before the big run.
In Dec we read that rabbits had been ordered. In Jan we read that rabbits had arrived but the wording was somewhat ambiguous and it wasn't clear they had been acclimatized (2 weeks). So in the best case scenario the rabbits were received mid-Dec and ready to dose first week of Jan. Add 2 weeks to grow tumors and 10 days of containment. The arithmetic is simple. At best the study has just been completed.
If they didn't use fresh cells and need 2 rounds of inoculation and if the tumors are a little sluggish to grow (it happens) then the containment study may not even have started. Hopefully Dr K will give us enough info tomorrow to figure out where the study is at.
Most optimistic timeline:
Tumor growth to treatable size from fresh VX-2 cells: 2 weeks
Containment study: 10 day
Data analysis: 1 week
Report drafting/reviewing/finalizing: 2 weeks (JHU is not a CRO that does this all the time)
I doubt it is happening that fast (I help design/monitor/analyze/report similar non-clinical studies for a living).
I take comfort in the fact that while we are wasting our time with him (he will never change), Dr K is busy getting RDGL ready for a successful IDE submission.
Yes, published in 2021. But doesn't mean the work was done in 2021. Read carefully.
Yes, but they are likely to get some quantitative data this time: X% intratumor retention Y% migration to margins/nearby tissues, Z% to other tissues. Will the FDA cap the radioactive dose administered? Will they feel uncomfortable to dose thyroid tumors and steer to other cancers where migration is less an issue? I don't know.
I expect a neutral Jan update like " We are completing studies needed for IDE submission".
Unlike what some say, RDGL has followed FDA recommendations. There might have been scientific disagreement but there was no resistance. Based on the successions of events and the meeting summaries provided it is highly unlikely that the FDA proposed a containment study design when the draft IDE was discussed. We know the containment and related dosimetry topics were discussed and FDA/RDGL agreed to a follow-up focused meeting. It would appear that not all available data had been submitted in the draft IDE since more material was sent to the FDA ahead of the May 22 meeting (based on a 1Q tweet). The FDA must have sent a written response before the meeting which alerted RDGL that the dataset was somehow lacking in FDA's opinion, which prompted RDGL to design a protocol to address the issue. But nobody knows exactly what the FDA wanted to see and for what purpose.
I doubt the FDA will ask for more studies. The rabbit VX-2 data is going to be "what it is". We have not been given any detail as to how the FDA will use the data.
Here is the most favorable timeline for Phase 1 of the rabbit study:
Inoculation (with fresh VX-2 cells): ~ Jan 3th
Tumors of treatable size and Radiogel application: ~ Jan 17th
End of containment study: ~ Jan 27th
I doubt it went that fast.
That I don't know. The next financial report may give us a rough estimate of how far they can go.
Here's an example of typical fees for a clinical trial (not from Mayo, but should be similar):
https://icts.uiowa.edu/sites/icts.uiowa.edu/files/wysiwyg_uploads/Study%20Start%20Up%20Fee%20Schedule.pdf
It doesn't require a huge budget to get things started and enroll 2-3 patients.
Definitely not. However, I would not be surprised if Dr K has investors ready to jump in after IDE approval.
Given that Radiogel is close to final design, transitioning to a pivotal trial from the EFS is a possibility. Enrolling 12-15 patients for the EFS may not take too long and we could know by 4Q 2024 (or earlier if enrollment is fast).
2.3 What Happens After an EFS?
(from: https://mdic.org/wp-content/uploads/2020/08/MDIC-EFS-Blueprint-for-EFS-Success-2016.pdf)
Different scenarios are available to the Sponsor/Innovator after completion of the EFS:
1) The Sponsor/Innovator in consultation with FDA may determine that further changes are necessary to optimize the device design, its deliverability, or technique of operation. In this case, an expansion of the EFS may be requested under the same Investigational Device Exemption (IDE);
2) The Sponsor/Innovator in consultation with FDA may determine that the design of the device is near-final or final, that adequate nonclinical data are available, and that the observations made in the EFS support the proof of principle that was aimed for with an acceptable safety profile. In this case, there might be enough information to provide a favorable benefit-risk profile to support the conduct of a traditional feasibility study.
Of note, it may be appropriate to move directly to the pivotal study if the preliminary safety and effectiveness information is adequate to define the pivotal study population, the study endpoints, and that the benefit-risk profile is favorable. This decision should be reached in collaboration with FDA.
A similar procedure could be happening (or will happen soon) at JHU...
Keeping it real:
Mid Jan 21: Feedback from FDA on BDD
Mid Sep 21: Draft IDE and meeting request submission
Sometimes between Jan and Sep RDGL received recommendation from the FDA to pursue EFS path and RDGL drafted IDE. Writing an IDE (or IND) takes time. Depending on the complexity and the number of external partners involved, it can take 3 to 6 months (see https://www.fda.gov/medical-devices/investigational-device-exemption-ide/ide-application for all that is required). RDGL had to rely on manufacturers, clinicians, etc... to gather all information needed. Add to this several rounds of reviews by multiple parties/consultants with their own timelines/availabilities and it can easily stretch to 6 months.
Those who claim Dr K didn't do anything towards IDE for 9 months in 2021 live in an alternate reality...
"hence FDA's suggestion at the first meeting"
Were you at the meeting? You don't know what the FDA suggested at that time. You are speculating and presenting as fact to fit your narrative.
The FDA may ask for information but they rarely tell you how to run studies (technical details). This is up to the sponsor.
Given the number of rabbits on study (26), Battelle may have chosen to propagate the VX-2 tumors in donor rabbit livers first to generate more cells for transplantation to hind limb. Unfortunately, I can't find info on yields from direct inoculation of cryopreserved VX-2 directly in liver vs inoculation in hind limb, as is more typically done (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463275/#b20-dir-20-4-335) to validate the approach. But there is no reason why this can't be done.
The purpose of the May20 meeting with the FDA was to discuss containment and dosimetry. The data in the 2021 paper is most likely what was used to support the latter, and obviously from the meeting update was ok'd by the FDA.
For the containment imaging, my guess if that the FDA is looking for more PET data than are available from the cat and dog study which clearly showed containment (see Fig 3 in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044762/). Unfortunately we don't know exactly what they are requesting, and for what purpose.
By looking at the published data it is clear that the Y-90 particles are contained and I can understand RDGL's frustration. I have been in similar situations before where we had disagreement with the FDA. At the end we had to cave in, despite having greater expertise on our side. I have former colleagues who are now reviewers with the FDA. Although they were good scientists, they were neither the most experienced nor the most knowledgeable ones we had in our department. Dr. Fisher may well have more experience than the FDA team combined.
"I never said that meant he grew them in a rabbit liver, but rather that these VX2 tumors are descended from a liver cancer"
This is what you actually said:
"In Dr. Fishers study the liver tumors were transplanted to and grown in muscle"
which is very different from:
"these VX2 tumors are descended from a liver cancer"
Which you really didn't say! You can't change your story as you go along.
Also, Dr Fisher did not identify VX2 as liver cancer cells. "VX-2 liver tumors" means VX2 cells having formed tumors in liver. Just like VX-2 lung tumors are VX-2 cells having formed tumors in the lung.
My beef remains with you.
More nonsense!
Here is one:
"In Dr. Fishers study the liver tumors were transplanted to and grown in muscle"
Dr Fisher never grew liver tumors and transplanted them. That is not how it is done (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463275/). Tumor cell propagation is in hindlimb muscles (donor rabbits). The next step in recipient rabbits is in almost any organ/tissue of choice. The VX2 cells are quite versatile.
It takes 2 weeks to grow 2 cc sized VX-2 tumors in the liver (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9128410/)
0.2 cc is the limit of tumor detection by PET (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590963/)
Measurement of radioactivity in excised tissue is a direct method to assess tissue distribution (I've done many more times that you have!). It is also far more sensitive and better suited to quantitatively measure leakage to distal organs, one of the main purpose of Dr Fisher's study.
From Dr Fisher's 2021 paper (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996238/pdf/hp-120-510.pdf) it only takes 2 weeks to grow treatable tumors from fresh cells:
Tumor cell harvesting and implantation
Tumor cells were harvested from among the 12 euthanized donor rabbits. A volume of VX2 carcinoma suspension was injected into the vastus lateralis muscle of each of 26 recipient rabbit’s left hind limb using aseptic techniques. Tumors in recipient rabbits developed thereafter in about 14 d and were ready for treatment.
So if the tumors from last summer have been propagated and fresh cells were available when the study rabbits arrived then the containment study per se may be on-going and data available by the end of the month. If not, then we need to add 3 weeks to this optimistic timeline and data could be available by the third/fourth week of February.
For an inept and inexperienced guy, Dr K did a pretty good job transforming a company from the brink of bankruptcy to a company with an improved product with optimized transportation and administration accessories, an increasingly robust patents portfolio, collaborations with top-tier clinical and veterinary universities, and support/recommendation from the FDA to test its product in an EFS.
Why would anyone invest in a company that is developing a product invented by some scientist who doesn't know what he is talking about and whose CEO is inept and wasting millions of $ every year?
Sorry, but the study is not done yet. It takes at least 3 weeks to grow the tumors plus 10 days for the containment assessment.
There is a possibility that Phase 1 and Phase 2 are part of the same study:
Phase 1 is 10 days of PET analysis for assessing containment, followed by Phase 2 (in the same rabbits) to monitor tumor shrinkage/resorption over a much longer duration, maybe 1-2 months.
The FDA may only need results from Phase 1 for the IDE. Phase 2 may have been added in later and is definitely a nice to have.
Unfortunately we were not given any details so we are left guessing.
My guess is that the FDA wants a "clean" containment study. All the PET data to date were in different species and tumor type/size. The VX2-rabbit will do that: Same species, tumor type and size. The results/conclusions will be the same but now they can include a mean and a standard deviation... I can understand RDGL's frustration.
Whoever claims that containment has to be 100% has never developed an oncology product! This is pure nonsense.
Someday the IsoPet treatment locations map will like this one:
https://www.synovetin.com/treatment_centers