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What do you mean 'nothing to talk about'? Have you forgotten 21st November already?!

An interesting discussion. Thanks for posting it.

Only 8 more sleeps...

21st is a Tuesday. Alan loves a Tuesday. You have been told. 😉

Excuse me. Are you saying that "the UK Health Secretary has just announced plans to streamline the drug approval process in the UK" and that that information is behind a paywall?

Government announcements come either a press release or item on their website to everyone or as a briefing to their friends. The latter are dodgy as the government is usually trying to spin the narrative. Telegraph was it?

And a 'regenerated' response (excluding the given point of targetting):

Precision Medicine Potential:

The absence of an MTD may indicate that the drug can be administered at doses effective against the cancer cells while sparing normal tissues. This aligns with the principles of precision medicine, where treatments are tailored to the individual characteristics of the patient and the tumor.

Reduced Systemic Toxicity:

If the drug is effectively localized to cancerous tissues through FAP targeting, it may result in lower systemic toxicity compared to traditional doxorubicin. This could lead to improved tolerability and fewer side effects for patients.

Challenges in Dose Optimization:

While the absence of an MTD is generally positive, determining the optimal dose that achieves the best balance between efficacy and safety is still crucial. Careful dose optimization and monitoring in later phases of clinical development will be important.

Long-Term Safety Assessments:

Even though the drug may be safe in the short term, long-term safety assessments should be conducted to ensure that the absence of an MTD doesn't lead to cumulative toxicities over extended treatment durations.

Patient Selection Criteria:

The lack of an MTD may prompt consideration of specific patient selection criteria, such as biomarkers or characteristics that predict responsiveness to the drug. This could contribute to more personalized and effective treatment strategies.

Regulatory Evaluation:

Regulatory agencies will likely scrutinize the safety and efficacy data closely, as the absence of an MTD might deviate from traditional dose-finding approaches. Comprehensive data on the targeted delivery mechanism and its impact on efficacy and safety will be crucial for regulatory evaluations.

Post-Marketing Surveillance:

Even after regulatory approval, post-marketing surveillance will be important to monitor the long-term safety and effectiveness of the drug in a larger patient population.

In summary, the absence of an MTD in a FAP-targeted pro-doxorubicin drug, while generally positive for safety, brings challenges in optimizing the dose and understanding the long-term effects. The targeted delivery mechanism, if effective, could offer advantages in terms of reduced systemic toxicity and improved precision in treating cancer. The development team and regulatory agencies will need to collaborate closely to address these considerations and ensure the drug's safety and efficacy in subsequent phases of development and post-approval.

"Regulatory discussions" to resolve the conundrum of no MTD... Longterm monitoring (after pivotal Phase 2 study)... Excellent stuff!

Breakthrough therapy designation incoming!

...safety, and regulatory discussions. The targeted nature of the drug provides a potential advantage in minimizing off-target effects, but ongoing monitoring and further clinical investigation are crucial as the drug progresses through development stages.

"What does it mean for a novel FAP-targetted pro-doxorubicin drug if it is efficacious and safe but no maximum tolerated dose is found?"

This was the repsonse (with apologies beforehand for LSE's atrocious formatting):

If a novel FAP (Fibroblast Activation Protein)-targeted pro-doxorubicin drug is found to be efficacious and safe but no maximum tolerated dose (MTD) is identified, it raises several important considerations specific to the nature of the drug and its targeting mechanism. Here are some potential implications:

Targeted Delivery Advantages:

The lack of an MTD might suggest that the FAP-targeted pro-doxorubicin drug allows for selective delivery to cancer cells expressing fibroblast activation protein without causing excessive toxicity to normal tissues. This is a positive aspect, indicating targeted therapy advantages.

Reduced Off-Target Effects:

The absence of a clear MTD could imply that the drug has a more favorable safety profile by minimizing off-target effects on healthy tissues. This is particularly advantageous in cancer treatment to reduce side effects associated with traditional chemotherapy.

Potential for Higher Efficacy:

If the drug is safe at all tested doses, there may be room for exploring higher doses to assess whether increased efficacy can be achieved without compromising safety. This could be especially relevant in the context of cancer treatment.

Individualized Treatment Strategies:

The targeted nature of the drug may open avenues for individualized treatment strategies, tailoring doses based on specific patient characteristics or the tumor microenvironment.

Challenges in Dose Optimization:

While the absence of an MTD is generally positive, determining the optimal dose for balancing efficacy and safety is still crucial. Close monitoring and dose optimization may be necessary in later phases of clinical development.

Exploratory Nature of Phase 1 Trials:

The early phases of clinical development, such as Phase 1 trials, are often exploratory and focus on safety. The lack of dose-limiting toxicities may reflect the specificity and selectivity of the drug but requires validation in larger patient populations.

Long-Term Safety Considerations:

Even with positive safety findings in early trials, the long-term safety of the FAP-targeted pro-doxorubicin drug should be carefully monitored, especially as patients may be on prolonged treatment regimens.

Regulatory Considerations:

Regulatory agencies will likely require comprehensive safety data and a thorough understanding of the targeted delivery mechanism. The absence of an MTD might necessitate specific discussions with regulators to determine appropriate dosing strategies.

In summary, the lack of an MTD for a novel FAP-targeted pro-doxorubicin drug, while generally positive, requires careful consideration of dose optimization, long-term saf

It would be good to have the C7 data included if that meant a higher initial dose for the fortnightly study. Time lost there would be about equal to time gained in Phase 1aV2 or higher final dose level at the end of Phase 1aV2. I would accept that as justification for the promised Phase 1a data release slipping into Q1 next year, but I doubt that Avacta would make that change as timeline slippages and unmet promises are already a problem for them, plus the way to present the full study data is, as AS stated, ideally in a peer review journal or a significant conference.

It should be remembered that that statement made at the AGM in June was at a time when it was planned that there would be a Phase 1b study.

That changed officially with the 19 September RNS announcing the completion of C6 and intention to apply for authority to do a fortnightly dosing Phase 1a study, to aim for a pivotal Phase 2 in 2024 and the statement that "Detailed Phase 1a data expected to be released in Q4 2023."

"The drug candidate is an affimer conjugated to pro-doxorubicin. It acts by targeting FAP. The drug candidate is developed based on the Tufts technology and pre|CISION technology ."

Hmm... that $500 would be better invested in more Avacta shares!

Yes. I didn't include considerations about publicity because that is content for another audience (investors, particularly retail investors) but, additionally, self-publishing gives complete control over the timing and content of the narrative.

Thank you Bella. I know AS has spoken in the past about publlishing the Phase 1a data in a peer review journal but circumstances have changed since he said that. Personally, I can't see Avacta publishing the promised Phase 1a data as a peer reviewed paper for a couple of reasons.

Firstly, timewise, it wouldn't be possible to do so before the end of the year as it takes about 6 months to go the peer review publishing route and AS has committed to publishing before the end of the year. The optics for Avacta would look very bad if the first publication of Phase 1a data was in Q2 of next year as AS will have known the realistic publishing timelines when he stated that deadline - and, more importantly, serious investors will know that he would have known that and was therefore promising something unattainable.

Secondly, what will be published will be interim data - a progress report, if you like - as it will contain results from C1-C6 only. Peer review will wait, I think, until the C7 data can be included, so I'd say that would be sometime around midyear next year.

Other options to present the data are at a conference or self-publishing.

A conference presentation with Q&A in front of an audience of peers takes time to get organised (prepared, submitted and accepted) so I think we are at the absolute limit or past the limit, even for late reporting data.

A conference poster again takes time to get included in the conference schedule but is a possibility - again, incredibly tight deadline for doing that.

Self-publishing is not as vain as it might sound and is, I think a definite possibility for the data from C1-C6, the reason being that Avacta will have prepared and QC'd all the data for presentation to the FDA and any acceptance of a fortnightly dosing regimen by the FDA will be done after considering the 3-weekly data so far collated and presented. Thus, my belief (and it is only my belief) is that publication of the C1-C6 data will be announced by RNS and appear on the Avacta website just after, if not at the same time as, the announcement of the go ahead for the fortnightly dosing study - with an explicit link being made between the two events.

The purpose of publishing the trial data afterall is for interested parties (pharma companies and specialist investment funds) to see the data so far and look through it all themselves (doing their own peer review of it), knowing that the FDA has been all over it already and effectively 'approved' it all.

British Journal of Cancer (BJC) - have I missed an important announcement?

↓ The projection is strong in this one

@Doggy100, How do you think clinical trial data is announced?

Thanks for the update but we really don't need to know about your hamburger endurance habit.

Cool it! Sujood is just Andy Wyndrum's parody account.

What's up matey? Dunning–Kruger effect wearing off?