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This shows you AVA6103 is worth billions once safety and efficacy is proven.

But Daiichi made more money licensing the out exatecan derivatives.

Daiichi Pharmaceutical Co., Ltd. (now Daiichi Sankyo) got the furthest in attempting to bring exatecan (DX-8951f) to market, taking it through Phase I, Phase II, and into Phase III clinical evaluations. 

If Daiichi Sankyo had successfully brought exatecan to market as a standalone drug (rather than as a payload in their DXd ADC platform), its value would have likely been substantial but hampered by early toxicity challenges. However, the strategic pivot to using exatecan derivatives in Antibody-Drug Conjugates (ADCs) led to a much higher valuation through partnerships with AstraZeneca and Merck, with potential deal values reaching up to $22 billion for specific, similar technology. 

Here is the breakdown of the value associated with Daiichi's "exatecan" efforts:

* Initial Exatecan (DX-8951f): Early trials for exatecan as a standalone drug showed promise but faced challenges with dose-limiting toxicities, including neutropenia and gastrointestinal effects. While it was determined to be a strong topoisomerase I inhibitor, its failure to establish a broad, safe therapeutic window as a standalone treatment limited its initial market value.

* The "Exatecan Derivative" (DXd) Revolution: Daiichi Sankyo realized the potential of exatecan by developing it into a "payload" (DXd) for ADCs. The success of this strategy is best represented by Enhertu (trastuzumab deruxtecan), an exatecan derivative ADC developed with AstraZeneca.

* AstraZeneca Deal (Enhertu): In 2019, AstraZeneca agreed to pay up to $6.9 billion to co-develop Enhertu.

* AstraZeneca Deal (Dato-DXd): In 2020, another deal worth up to $6 billion was signed for a second ADC, Dato-DXd.

* Merck Deal (3 ADC candidates): In 2023, Merck entered a deal worth up to $22 billion for three of Daiichi’s other DXd-based ADCs. 

*

If exatecan had been successfully launched earlier as a targeted, safe treatment, it would likely have rivaled or surpassed other topoisomerase-based therapies. Its successful adaptation into DXd, however, created a much larger, multi-billion dollar impact on Daiichi Sankyo’s market capitalization.

Good luck all

Keep hold of your golden shares.

T. W. A. T. ‘s

T horn. W ynd. A nd T ouk

Can you close the door after yourselves

BV is right for P1a and P1b

it only works out 36 patients per indication

4 x cancer types.

Getting a biotech clinical trial selected by NEXT Oncology is highly competitive, as they are a premier Phase I network looking for novel, high-potential agents. However, it is not "hard" in terms of bureaucracy if the trial aligns with their mission of accelerating innovative, "next-generation" cancer treatments for patients who have exhausted other options. 

As of 2025, NEXT Oncology is part of the IQVIA family and is strongly partnered with Texas Oncology (the largest private oncology practice in the US) and Crown Bioscience, focusing heavily on Phase 1 trial innovation. 

Factors Affecting Selection Success:

* Novelty and Type of Agent: NEXT Oncology prioritizes novel drugs that augment the immune system or target precise molecular markers, specifically looking for new treatment options for patients whose current therapies are no longer working.

* Scientific Merit & Data Quality: They require high-quality translational data, often utilizing patient-derived models (PDX and organoids) in collaboration with Crown Bioscience to validate candidates.

* Speed and Efficiency: They emphasize fast, "real-time activation" for patients. Adoption of technology like proXimity™ for near real-time data transmission to Electronic Data Capture (EDC) systems makes a trial more attractive, as it speeds up decision-making.

* Partnership Network: Their affiliation with Proxima Clinical Research's Early Phase Oncology Network (EPON) indicates that partnering with experienced CROs in their network can streamline the selection process. 

*

How to Increase Chances:

* Align with Phase 1 Focus: Focus on novel therapeutics (e.g., targeted therapies, immuno-oncology) that meet unmet needs.

* Demonstrate High-Quality Preclinical Data: Provide robust evidence of safety and efficacy.

* Emphasize Rapid Startup Capability:Trials that can demonstrate quick, efficient startup processes are preferred.

* Engage through Existing Networks: Work through their partner networks (e.g., IQVIA, Proxima CRO, US Oncology Network). 

*

While they run over 100 trials, the high demand for top-tier Phase I sites means they are selective based on the potential impact on patient care

Phase 1a (Dose Escalation): The dose-escalation portion is designed to evaluate the safety, tolerability and MTD and/or RP2D of AVA6103, administered as monotherapy in two schedules: Day 1 of a 21-day cycle (Q3W schedule) and Day 1 of a 14-day cycle (Q2W schedule).

Inclusion Criteria:

12. The subject is willing and able to comply with the protocol, including any PK blood sampling and tumor biopsy requirements and agrees to return to clinic for follow-up visits and examinations.

But then says:

For subjects in Phase 1a or 1b, on treatment tumor biopsy is optional. -

https://clinicaltrials.gov/study/NCT07454642

If tempus AI has already screened patients can trial start straight away.

Yes, in many cases, a patient can be dosed very quickly after recruitment—sometimes within days—if Tempus AI has already screened and identified them, thanks to specialized, rapid-activation trial models. 

While traditional trials can take months to activate, the Tempus TIME Program uses an AI-powered platform (TApp) combined with rapid operational procedures to facilitate accelerated enrollment and dosing, often in a "just-in-time" (JIT) model. 

Key Aspects of Rapid Dosing with Tempus AI:

* Pre-screening & AI Matching: Tempus AI uses artificial intelligence (TApp) to screen patient EMR data (including structured and unstructured clinical notes) against trial protocols daily.

* Nursing Review: Before the site is notified, Tempus AI nurses review these AI-identified matches to confirm eligibility.

* Just-In-Time (JIT) Activation: When a match is confirmed, the site can trigger a JIT activation, which includes pre-negotiated contracts, rate cards, and central IRB approvals.

* Rapid Dosing: Studies have shown that with this process, sites can be activated in a few days, and patients can be dosed within 10 days of being identified as a match.

* 
Limitations to "Immediate" Dosing:

While the screening is "pre-done," a patient cannot be dosed "immediately" (i.e., in minutes) upon walking in. Certain regulatory and medical steps must occur after the patient is matched: 

1. Informed Consent: The patient must provide signed, informed consent before any study-specific procedures can occur.

2. Confirmatory Screening: The clinical site staff must still confirm the patient meets all inclusion/exclusion criteria.

3. Baseline Assessments: The protocol may require baseline lab tests or imaging to be done before the first dose is administered. 

4.

In summary, Tempus AI removes the long delays of site activation and identification, allowing patients to be dosed much faster—often within days—rather than weeks or months. 

Every BP that has tried to tame Exatecan will be watching…

Who moves first

Keep hold of your golden shares…

“ delivering sustained release of exatecan in the tumor microenvironment with potent antitumor activity”

GLA

What happens if Phase 1 data replicates the mouse results?

Clinical proof-of-concept like this would trigger a massive re-rating because:

1. PoS for AVA6103 jumps sharply — from 15% to 50–70%+ (comparable to how AVA6000’s orphan indication got 60% PoS after early signals). That alone multiplies the asset’s rNPV contribution several-fold.

2. Platform validation — The entire pre|CISION® technology (applicable to ~90% of solid tumours) gets de-risked. Trinity and other analysts would upgrade the platform placeholder dramatically.

3. Commercial/comparables upside — Exatecan is the same payload class as in Enhertu (peak sales forecasts $10–12bn). AVA6103 targets FAP (far broader than HER2) with better preclinical selectivity and sustained release. Strong data would scream “potential best-in-class” and attract big-pharma licensing or buyout interest.

4. Market psychology — Biotech stocks routinely 3–5× (sometimes 10×) on spectacular early efficacy. Phase 1 CRs or high ORRs in refractory patients are rare and trigger hype, follow-on financing on better terms, and accelerated timelines.

Resulting valuation math (illustrative, based on Trinity’s framework):

• AVA6103 contribution today: low tens of millions (placeholder).

• Post-data: easily £500m–£1bn+ (higher PoS × higher peak sales × derisking).

• AVA6000 and platform also rerate upward.

• Total rNPV could reach £1.3–2.2 billion+ (300–500p+ per share).

Markets often overshoot rNPV on positive news, so 500p+ isn’t crazy if a partnership is announced alongside the data. Cash runway (into Q3 2026) and potential NASDAQ listing would help too.

Realistic ranges in this scenario:

• Base / moderate replication (good ORR + safety but not perfect CRs): 200–300p (still a huge win, market cap ~£900m–£1.3bn).

• Strong replication (multiple CRs/durable responses confirming mouse data): 300–500p.

• Moonshot (CRs + big-pharma deal): 600p+ or buyout premium (rare but possible).

Bloody hell gents just used the ones that spelt LAMBS 😂

All the LAMBS have invested heavy in ADC’s they need Pre/Cision

Who makes the first move once the data room shows first results for AVA6103 in humans.

BP all watching, repeat the mice results in humans and Bidding war starts.

They are all Silent now but not much longer :

L illy

A stra Zen

M erck

B ristol MS

S anofi

GLA

“I think it probably not lost on anyone in this room or at this conference the kind of explosion of business development activity, licenses, partnerships that’s happened over the last few years and, you know, one of the exciting things for us is, you know, it’s a whole new market that is creating new royalties, right? When you look at what these are, these are, you know, royalties in the hands of multinational pharma companies that are being paid to a, you know, kind of biotech innovator.”

Bella could be right,great fireside chat on the day Avacta were moved to next day read below:

https://uk.investing.com/news/transcripts/royalty-pharma-at-td-cowen-conference-strategic-growth-insights-93CH-4539210

Lilly Evens

Novartis 6/4

AZ 2/1

Merck 5/2

Avacta taken out this year 1/3

GLA

I have put all our resident trolls in the green bin so reading this BB is so peaceful.

But I see there are a few still active on “X”.

Avacta are making fantastic progress with Pre/Cision,but some still worry about financials. I said the other day,

I expect Richard Hughes and his investors to participate with another private listing to leverage T/O or partnership negotiations and to secure sign off on accounts.

Why worry about financials at this stage.

Does anyone think that Richard Hughes one of the most experienced investors in the UK and founder of Zeus who knows all the tricks of the AIM market, would actual risk his own money and his close friends, family and colleagues ( millions on the last two private placings ) to just let Avacta go into liquidation.

2026 will be the year just hold as tight as possible to your shares.

GLA

If a more powerful, cheaper and miles safer drug comes along that will take your market share and sales of £14 billion.

You can’t sit and watch a rival snap it up.

Daiichi Sankyo and AstraZeneca experienced significant, well-documented safety issues regarding toxicity during the clinical trials for Enhertu (fam-trastuzumab deruxtecan-nxki), particularly involving interstitial lung disease (ILD) and pneumonitis. While the drug showed high efficacy, these toxicities necessitated careful management and resulted in fatalities in early studies. 

1. Interstitial Lung Disease (ILD) / Pneumonitis 

* The Major Problem: ILD, characterized by lung inflammation or scarring, was identified as a significant, potentially fatal adverse event of special interest.

* Fatal Cases: In early trials (such as DESTINY-Breast01), drug-related ILD resulted in death for approximately 2.2% to 2.6% of patients.

* Incidence Rates: In a pooled analysis of nine Phase 1 and 2 trials, the overall incidence of drug-related ILD was 15.4%.

* Trial Specifics: Rates varied by trial, with 10%–14% in breast cancer studies and higher rates reported in early lung cancer trials.

* Management: The high rate of ILD led to mandatory, rigorous monitoring protocols, including potential discontinuation of the drug for Grade 2 or higher ILD. 

2. Other Key Toxicities and Safety Issues

* Fatalities: Beyond ILD, fatal adverse reactions in clinical trials included sepsis, cardiac arrest, pneumonia, and general physical health deterioration.

* Discontinuation Rates: In trials, roughly 9% to 16% of patients permanently discontinued treatment due to adverse reactions, with ILD being a leading cause (accounting for 6%–10% of discontinuations).

* Dose Interruptions: High rates of dose interruptions (up to 39%–62% of patients in some trials) were necessary to manage toxicities.

* Common Side Effects: The most frequent adverse reactions (≥20%) included nausea, low white blood cell count (neutropenia), low red blood cell count (anemia), fatigue, vomiting, alopecia, and diarrhea.

* Cardiotoxicity: While less frequent than ILD, Decreased Left Ventricular Ejection Fraction (LVEF) was observed, with studies reporting incidence rates around 1.9% to 3.8%. 

3. Mitigation Efforts

* Dose Optimization: Studies like DESTINY-Lung02 showed that using a lower dose (5.4 mg/kg) resulted in a significantly lower rate of severe ILD compared to higher doses, which helped refine the approved dosage.

* Adjudication Committees: The companies used independent committees to rigorously review all potential ILD cases, refining, and understanding the risks better over time. 

Despite these toxicity issues, the benefit-risk profile for Enhertu was considered positive by regulators due to its high efficacy in previously treated, heavily pretreated, or advanced cancer patients. 

IMO

Richard Hughes and his investors will buy another private listing tranche of shares, just enough to get sign off and see AVA6103 initial results.

Then it’s over to BP for the bidding war..

Why license when the BP winner will buy the farm.

GLA

Keep hold of your golden shares…..

Enhertu Sales Projections for 2033 and Beyond

Peak Sales Estimates: Analysts at GlobalData project Enhertu sales could reach $13.9 billion by 2030. Other industry forecasts suggest peak annual sales could ultimately range between $14 billion and $15 billion before the main patents expire in 2033.

Big chunk of them sales would collapse with safer and stronger and cheaper drug rival coming …

GLA

Grok must have this wrong then :

They have started the FiREBOLT trial (NCT07213791) which is Eli Lilly’s flagship study for LY4337713 (formerly 177Lu-PNT2004), a radioligand therapy that uses Avacta's pre|CISION® chemistry to target Fibroblast Activation Protein (FAP). into active recruitment phases at multiple sites, including major centers like Duke University Hospital now in early 2026.

Clinical Objectives

1. Dose Escalation (Phase 1a): Identifying the Maximum Tolerated Dose (MTD) and evaluating how the drug is absorbed and cleared from the body.

2. Dose Expansion (Phase 1b): Testing the optimized dose across specific tumor types, including:

* Pancreatic adenocarcinoma

* Various breast cancers (HR+, HER2+, and Triple Negative)

* Ovarian, gastric, colorectal, and esophageal cancers.

3. Endpoints: The primary focus is safety and tolerability, with secondary measures for Objective Response Rate (ORR) and Duration of Response (DOR) monitored over a 5-year period. 

Why It Matters

By using the pre|CISION "masking" technology, LY4337713 aims to deliver Lutetium-177 radiation specifically to the tumor microenvironment, sparing healthy tissues and potentially overcoming the toxicity limits of traditional systemic radiotherapy. 

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Lilly have an early advantage over other BP they already have a Pre/Cision licence.

They have started the FiREBOLT trial (NCT07213791) which is Eli Lilly’s flagship study for LY4337713 (formerly 177Lu-PNT2004), a radioligand therapy that uses Avacta's pre|CISION® chemistry to target Fibroblast Activation Protein (FAP). into active recruitment phases at multiple sites, including major centers like Duke University Hospital now in early 2026.

If they start to see outstanding results they could make a move for the whole of Pre/Cision.

But do other BP sit back and let them….

The license agreement between Avacta Group and POINT Biopharma (now an Eli Lilly subsidiary) is a multi-asset deal focused on tumor-activated radiopharmaceuticals. 

Milestone Triggers

The financial structure is tied to the clinical and commercial progress of the pre|CISION® platform: 

* Primary Asset (PNT2004 / LY4337713): Avacta is eligible for up to $9.5 million in combined upfront fees and development milestones. As of late 2025, an estimated $5–7 million of this remains, with potential triggers tied to Phase I dosing in the FiREBOLT trial.

* Pipeline Expansion: For each additionalradiopharmaceutical prodrug developed using the technology, Avacta receives up to $8 million in milestones.

* Commercial Success: The deal includes low-single-digit royalties on net sales and a percentage of any sublicensing income generated by the assets. 

Exclusivity Rights

Lilly holds a hybrid license that balances broad platform access with specific protection for their lead programs: 

* Exclusive Rights: Lilly (via POINT) has exclusive rights to the pre|CISION technology for the specific radiopharmaceutical prodrugs it develops (e.g., PNT2004/LY4337713).

* Non-Exclusive Rights: Lilly also holds a non-exclusive license to use the broader platform for developing a pipeline of FAP-activated radiopharmaceuticals.

* Avacta’s Retained Focus: Crucially, Avacta retains the rights to use the pre|CISION platform for its in-house focus on chemotherapy prodrugs (like AVA6000) and Peptide Drug Conjugates(like AVA6103). 

The FiREBOLT trial (NCT07213791) is Eli Lilly’s flagship study for LY4337713 (formerly 177Lu-PNT2004), a radioligand therapy that uses Avacta's pre|CISION® chemistry to target Fibroblast Activation Protein (FAP). 

Trial Overview

* Design: A Phase 1a/1b open-label, non-randomized study focused on dose escalation and optimization.

* Participants: Targets approximately 241 adults with advanced FAP-positive solid tumors.

* Status: The study was officially planned and submitted in October 2025. As of early 2026, it is moving into active recruitment phases at multiple sites, including major centers like Duke University Hospital. 

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