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Should actually be ferry docks.

In clinical trials, FPI (First Patient In) marks the critical milestone when the very first participant is screened, enrolled, and officially enters the study, signifying the transition from planning to active execution. It validates site readiness, kicks off data collection, and is a major KPI for project timelines and investor confidence.

Here are the key details regarding FPI:

Key Aspects of FPI

• Definition: It is the date the first human subject is qualified, accepted, and often dosed in a clinical trial.

• Significance: It proves all regulatory approvals, document reviews, contracting, and site setups are complete.

• Business Impact: FPI is a high-pressure corporate goal that affects company reputation, stock prices, and investor confidence.

• Trial Flow: It moves the study from "study start-up" to "execution/recruitment" phase.

Why FPI Matters

• Timeline Driver: It sets the pace for the rest of the recruitment and trial timeline.

• Success Indicator: Meeting the FPI goal on time usually means the study is on sound footing.

• Risk: Rushing to hit FPI dates can sometimes lead to neglected study designs or premature starts.

Sometimes, this milestone is also referred to as FPFV (First Patient First Visit), focusing on when data collection begins for that first subject.

The FDA has 30 calendar days to review an IND application after receiving it.

https://drugdevelopment.web.unc.edu/u-s-investigational-new-drug-application-%e2%86%92-ind-application-process/

IND submitted mid/late December (as per the project plan in Spotlight 13) and approved by 20 January. The FDA will have been working closely with Avacta given the experience with faridox so that was a fast turnaround given the US government shutdown gping on at the time.

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And ToucanOfDoom, stop purporting to know better than CC what the likely timescales are.

Https://avacta.com/research-development-spotlight-series-episode-13/ @26:15 FPI late Q1/26

Here are some links re Richard Jarvis at Novartis:

Richard Jarvis history: https://rocketreach.co/richard-jarvis-email_238424640

Richard Jarvis at Jarvis Advisors: https://www.moneyhouse.ch/en/company/jarvis-advisors-gmbh-5842690731 (Binningen is on the edge of Basel, home of Novartis HQ)

Richard Jarvis consultant: https://www.linkedin.com/posts/the-difference-collective_say-hello-to-collective-consultant-richard-activity-7389560479272259584-EiwK (with photo)

Richard Jarvis at Cohesion Bureau: https://cohesionbureau.com/bureau/richard-jarvis (with photo)

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And here is the Cohesion Bureau team at their various locations in Europe and the US: https://cohesionbureau.com/bureau

As the mechanism of action—the dipeptide and the cleavage—is proven, it now comes down to designing each molecule's pharmacokinetics to fit the needs for the warhead. And who better to lead that than a highy competent chemist at the top of his game?

We don't know what he was doing not why he's no longer on the team. He was another of Alan's hires that's now gone.

We'll know where and when in the fullness of time.

https://www.linkedin.com/in/michelle-morrow-127605137

A good decision. From CC's praise, he's likely been leading the science anyway.

Avacta's new comms organisation, based in Geneva: https://cohesionbureau.com/

It's All Change, every month, with Avacta!

The link didn't work so I ran that query in Grok. Yes, the procedure is involved but so is standard doxorubicin I should think - valid prescription, qualified people, the "Five Rights", etc. but with the added safety measures need for radioactivity.

I should think the patients have to be held in the hospital to be sure that the drug can be administered rather than have them just ambling in for the 3-weekly injection, the reason being timeliness, timeliness, timeliness...

to Grok: "What are the steps to get a radiopharmaceutical from production to patient?"

"The journey of a radiopharmaceutical from production to patient administration is a highly time-sensitive, regulated supply chain due to the short half-lives of most radionuclides (often hours to days). This limits the window for manufacturing, quality control, transportation, and use. The process varies depending on the radionuclide (e.g., cyclotron-produced like F-18, Ga-68, or reactor-produced like Mo-99/Tc-99m, Lu-177) and whether the product is a ready-to-use diagnostic agent (e.g., FDG), a kit requiring on-site labeling, or a therapeutic agent."

...and so it goes on with the 11 stages and summarised under Key Challenges (Time pressure, Radiation safety, Regulatory compliance, Supply chain complexity)

It's the two CanSEEK programs at the bottom of the pipeline list, the ones still in 'Discovery' in March 2024, that use the cleavable pre|CISION dipeptide. I can't remember how it works. I think it was JiveTurkey who explained it.

https://web.archive.org/web/20240308032516/https://www.pointbiopharma.com/our-products/pipeline

The FAP-targetting that POINT Biopharma were taking into the clinic was earlier Bachovchin tech that they had licensed.

bachovchin patents fap radioligand

https://www.google.com/search?q=bachovchin+patents+fap+radioigands

"AI overview: Dr. William W. Bachovchin and his laboratory at Tufts University are inventors on key patents regarding boronic acid-based FAP-targeting ligands and radiopharmaceuticals. These inventions form the basis of FAP-targeted radiotheranostics, notably including the compound PNT6555.

Here are the key details regarding Bachovchin’s work on FAP radioligands:

Key Aspects of Bachovchin’s FAP Patents & Tech

• Core Technology: The patents cover novel boronic acid-containing FAP-targeting ligands, specifically using a boroPro-based framework.

• Key Compound (PNT6555): PNT6555, a boronic acid–based FAP-targeted radiotheranostic, was synthesized based on work by Bachovchin et al.. It is designed for both imaging and treating FAP-positive tumors.

• Patent Scope: His work includes patents on FAP and other post-proline cleaving enzymes. One notable patent is US11707539B2, "FAP-targeted radiopharmaceuticals and ...".

• Partnership with POINT Biopharma: Bach Biosciences (associated with Dr. Bachovchin) licensed this pan-cancer targeting technology, known as canSEEKTM, to POINT Biopharma.

• Advantage of Framework: Compared to some other FAP inhibitors, these boronic acid derivatives have shown unique binding properties and are used to create targeted radiotheranostics.

Relationship to Other FAP Tracers

While Bachovchin’s work focuses on boronic acid scaffolds, it is part of the broader field of FAP inhibitors (FAPI), which also includes peptide-based agents like FAPI-04 and FAP-2286 developed by other groups.

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About canSEEK:

when did point biopharma sign an agreement with bachovchin

https://www.google.com/search?q=when+did+point+biopharma+sign+an+agreement+with+bachovchin

"AI Overview

POINT Biopharma announced that it entered into a definitive agreement with Bach Biosciences to license the canSEEK™ tumor-targeting technology on November 10, 2020.

Key details of the agreement included:

• Purpose: To acquire exclusive global rights to the canSEEK™ pan-cancer targeting technology for use in radiopharmaceuticals.

• Resulting Pipeline: The deal allowed POINT to expand its pipeline to include PNT2004.

• Partnership: Dr. William Bachovchin continued to develop the drug in partnership with POINT."

canSEEK™ seems to be the term for all Bachovchin's FAP-targetted radioligand tech, not just the cleavable pre|CISION tech: https://www.globenewswire.com/news-release/2020/11/10/2123598/0/en/POINT-Biopharma-and-Bach-Biosciences-announce-licensing-and-partnership-for-canSEEK-pan-cancer-targeting-technology.html

If it were we would surely have received a milestone payment which would have been RNS'ed...

As it is, the timeframe for [Lu-177]-PNT6555 doesn't fit with Avacta's agreement with POINT Biopharma anyway - agreement signed January 2021, Phase 1 started July 2022 and CanSEEK still being described as 'Discovery' in 2024.

OK, I've got it now. Here is the Lilly page for LY4337713: https://www.lillyoncologypipeline.com/molecule/Fibroblast-Activation-Protein-Radioligand

On the 'Molecule Overview' tab: "Clinical Development - LY4337713 is currently being studied in a Phase I clinical trial for patients with advanced solid tumors.3"

This is reference 3: https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS3161

AI Overview: "The reference describes the FRONTIER trial, an open-label, phase 1, dose-escalation study evaluating the safety, tolerability, and dosimetry of the Fibroblast Activation Protein inhibitor (FAPi) radioligand [Lu-177]-PNT6555 in patients with select solid tumors. This investigational agent targets FAP, often highly expressed in the stroma of various solid tumors."

So it looks like Lilly terminated the POINT Biopharma Phase 1 trial (FRONTIER) and started their own (FiREBOLT) but have yet to update their pipeline page. Anyway, not a CanSEEK candidate.

Not necessarily.

I misread the date. The FiREBOLT trial started in 2025 (2025-10-22).

But I was going from the association of LY4337713 with PNT2004 and I know that PNT2004 was in Phase 1 when POINT Biopharma was taken over and that their pipeline showed CanSEEK as being in preclinical: https://web.archive.org/web/20240308032516/https://www.pointbiopharma.com/our-products/pipeline (at 8 March 2024)

I can find no record of PNT2004 in the clinicaltrials.gov site but I can as 177Lu-PNT6555 (as PNT2004 was also known as in the POINT Biopharma pipeline): https://clinicaltrials.gov/study/NCT05432193 which was terminated (business decision).

So, what is LY4337713? This topic came up before: https://www.lse.co.uk/ShareChat.html?ShareTicker=AVCT&share=Avacta-Group&thread=CE8C21A1-94E9-409B-AE2E-7CE923C95C00 and it's not any clearer to me now than it was then but hopefully it is indeed a CanSEEK compound and Avacta get a timeline payment when the first patient is dosed.

LY4337713 (a form of PNT2004) is from the Bachovchin FAP tech that predates pre|CISION. The FiREBOLT Phase 1 study started in 2022: https://clinicaltrials.gov/study/NCT07213791

Lilly don't seem to be doing anything with CanSEEK, the radiotherapy version of pre|CISION. A question for Avacta at the AGM!

From the AACR-NCI-EORTC 2025 poster:

"The pre|CISION ® dual payload pipeline currently comprises two approaches:

• Combination of two distinct anti-cancer mechanisms with clinical activity: Microtubule inhibition and Topo I inhibition (MMAE and exatecan)

• DNA damage response (DDR) agents ATR or PARP inhibitors with exatecan: Inhibition of DNA repair potentiates the effect of exatecan"

https://avacta.com/wp-content/uploads/2025/10/AACR-NCI-EORTC-2025-Avacta-Dual-Payload-Poster.pdf

Has CC said what it will be? The website says "The dual payload pre|CISION platform was designed for the management of difficult to treat cancers by releasing more than one payload at the same time in the tumor microenvironment. The first molecules are designed with a potent topoisomerase I inhibitor and targeting the key resistance mechanism of DNA damage repair", which suggests just Exd+PARPi or Exd+ATRi.

Are there any anticancer candidates that are more potent than exatecan?

https://www.google.com/search?q=Are+there+any+anticancer+candidates+that+are+more+potent+than+exatecan%3F

Exatecan is a camptothecin derivative.

In short, there are more potent camptothecin derivatives: "Research indicates that some novel camptothecin analogs have demonstrated single to tens of picomolar (pM) IC50 potency, with specific tests showing some are more potent than exatecan"

...and payloads with different mechanisms of action that are potentially more toxic: "While exatecan is the king of TOP1 inhibitors, other classes of ADC payloads are generally considered "ultra-potent" (often in the low pM range):

• Pyrrolobenzodiazepine (PBD) Dimers: Known for extreme potency, these DNA alkylating agents can reach picomolar IC50 levels.

• Duocarmycins: DNA minor groove alkylators offering exceptional potency.

• Calicheamicin: Ultra-potent DNA-cleaving agents used in approved ADCs.

• Tubulysin Analogs & Cryptophycins: Novel microtubule inhibitors showing picomolar activity in pre-clinical studies.

Note that there will be many more that are so toxic that they are dropped without any mention of them in the public domain. And not being mentioned or demonstrated in the public domain goes a long way towards new compounds being patentable - the other main criteria is non-obviousness, but that's interpretted fairly laxly for new drugs.

I've been surprised so many times in th epast, I'm not going to predict what's 'in th epipeline' nor when we'll get to hear about it. I just think that it is far, far more likely to be positive news than negative.

It's important to bear in mind that there is a paradigm shift going on here: the rules of small molecule chemo have been completely upended and the extremely toxic preclinical, and earlier, candidates that would kill patients' organs before killing tumours can potentially now be used to attack just the tumours. Companies developing anticancer therapies are in a unique position within the industry because they want to find compounds that actually ARE the most toxic and what had been the hard problem of differential toxicity has just got a whole lot easier.

Pharma companies everywhere will have shelves and shelves in their fridges full of samples of highly toxic candidates that failed even in early animal testing, let alone preclinical. The question now is maybe "Which is the best target to go for in order to fully kill the cancer?"