Member Info for BuenaVista

Well I assumed the ToucanOfDoom meant end of Q4.

If Q3 was indeed meant, then what timelines did CC set for Q3? I'm only aware of these for AVA6000 and AVA6103: https://avacta.com/wp-content/uploads/2025/07/Avacta_Corp_23July2025.pdf (slides 20 and 29 respectively) and there are no Q3 deadlines there.

So, the evidence-based engineer, doesn't require evidence, just a 'feeling'?

Btw, do you have a clear vision of HEMO’s future by 1Q26? You do know do you that their Phase 1 trial is slated to run to 4 cohorts (plus the paediatrics) through to early 2027?

What's your evidence for believing that?

Big farmer is very conservative. Understandable when one considers the size of the deals and the magnitude of the consequences of failure. ADCs are the flavour of the decade because everyone is doing them so each farmer has as much chance of success as the next even if the improvements are only incremental. ADCs are 'proven' and accepted by the regulators, and thus safe. PDCs are an unknown quantity and thus 'risky'.

Alternatively - or maybe in conjunction - the Avacta business development team are just continually saying "You're having a laugh" and "Higher. Higher."

By now Avacta must have collected a lot of data, including more animal studies, about AVA6103 ahead of the planned IND submission at the end of Q4: https://avacta.com/wp-content/uploads/2025/07/Avacta_Corp_23July2025.pdf (slide 29).

The AACR-NCI-EORTC 2025 International Conference on Molecular Targets and Cancer Therapeutics will take place at Hynes Convention Center Boston, Massachusetts from 22 to 26 October. It was at last year's conference that the Avacta pipeline was unveiled and the initial AVA6103 data were presented.

https://avacta.com/wp-content/uploads/2024/10/EORTC-NCI-AACR-poster-AVP103-v1_SS44.09_V1.1-updated-18.10.24-003.pdf

So what's happening this year? Last year, Avacta announced on 10 October that it would be presenting three posters including a AVA6103 poster on 24 October. So we could get an announcement about attendance this year, which would surely include AVA6103 data, any time up to early October. Or we could get data presented at the interims at the end of September instead. Or, and the ToucanOfDoom will love this, AVA6103 has been killing all the test animals for months and CC & crew have been putting on a very brave face and BS'ing us with bravado whilst banking their salaries and ordering more ribena for NCT04969835.

😭

Stop insulting people and then playing the victim. It's a pathetic game.

Thanks. I had had a look with a couple of AI bots . They didn't find any link but did suggest looking for intermediaries as a link.

TW having a grudge is nothing new. The guy is a nasty piece of fascist sh ite.

@Aldebaran

What in the link that Tom Winnifrith is making between Ron Bauer and Cellin Technologies?

They won't talk about the full Phase 1a data until after Dr Tap has presented it at conference (19 October).

A question for next Tuesday's Q&A. The more people that ask it, the more likely they are to notice and maybe answer.

We'll know we've arrived when JungleVIP turns up with a Strong Buy opinion.😂😂😂

Https://n4pharma.com/nuvec

@LLP, yes you're right. I jumped in too soon. PQ203 has come up before here. If I remember correctly, it is a PDC that targets a receptor in cancer and releases the warhead by cleavage in an acid environment, namely the acid environment in the cancer. Off-target cleavage would cause side effects:

AI Overview

Acidic environments in the body include the stomach, the skin, and the bladder, all of which utilize a low pH for crucial functions like digestion and protection from microbes. Other potentially acidic areas are the vagina and urine, also serving protective roles. These acidic conditions are vital for specific physiological processes and are maintained through sophisticated buffering and regulatory systems, such as the body's ability to manage carbon dioxide levels through breathing.

Specific Acidic Environments

Skin: The skin has a natural pH between 4 and 6.5. This "acidic mantle" provides a protective barrier against harmful microbes and infections.

Bladder and Vaginal Area: Similar to the skin, these areas are also naturally acidic to protect against the overgrowth of invading microorganisms and maintain their health.

Urine: The pH of urine can vary significantly (4.6 to 8.0), but an acidic range helps limit the growth of bacteria in the urinary tract.

AI Overview

Acid environments in disease occur in two primary forms: Metabolic acidosis, where the body produces or retains too much acid (like in diabetic ketoacidosis or severe diarrhea), and Respiratory acidosis, where the lungs fail to remove enough carbon dioxide, leading to increased acidity (seen in conditions like severe chronic lung disease). Other diseases, such as Gastroesophageal Reflux Disease (GERD), can also be linked to abnormal acid exposure, particularly in the esophagus.

More details about acid environments in disease here: https://www.google.com/search?q=what+acid+environments+are+there+in+diseases

Disappointing that AVA6000 hasn't been fast tracked (yet). A question for 30 September.

PQ203 is an ADC so likely to have the side effects problems of ADCs. Pre|CISION is better all round.

The PDF of that patent: https://patentimages.storage.googleapis.com/96/0b/1d/a4294815b2e795/WO2024200988A1.pdf

VS, I believe that will be this patent family, including World patent WO2024200988:

Tnfr2 binding polypeptides and methods of use

Abstract

The present disclosure relates to engineered TNFR2-binding Stefin A polypeptide variants, polynucleotides encoding the engineered TNFR2-binding Stefin A polypeptide variants, cells expressing the polypeptide variants, pharmaceutical preparations of the polypeptide variants, and uses of the polypeptide variants in the treatment of various human conditions, including inflammatory, autoimmunity and cancer.

----------------------

I don't really know what's going on at AffyXell. I try to stay away from immunology as I find it far too complex. This is what Google responded to the 'question' https://www.google.com/search?q=affyxell+TNFR2 so if TNFR2 is "the second target of interest for AffyXell", then that is the patent family.

AI Overview

AffyXell's TNFR2 refers to its work in developing novel therapeutic antibodies for the Tumor Necrosis Factor Receptor 2 (TNFR2) pathway, which plays a role in immune regulation and autoimmune diseases, and its patenting of genetically modified cells that encode TNFR2 binding agents. TNFR2 agonists are being explored for autoimmune diseases and neurodegenerative conditions like MS, while targeting TNFR2 can also unleash anti-tumor immune responses.

AffyXell's Involvement with TNFR2

Therapeutic Development: AffyXell is involved in the development of therapeutic molecules that target the TNFR2 pathway, including antibodies with agonistic (activating) and potentially antagonistic (blocking) activity.

Genetically Modified Cells: The company has filed patents for genetically modified cells that encode TNFR2-binding agents, suggesting a platform for delivering TNFR2-targeted therapies.

The Role of TNFR2

Immune Regulation: TNFR2 is crucial for immune cell function, particularly for the stability and function of regulatory T cells (Tregs), which suppress immune responses.

Autoimmune Disease Therapy: Because TNFR2 agonists can expand and activate Tregs, they hold promise for treating autoimmune diseases by dampening excessive immune activity.

Neurodegenerative Disease Therapy: TNFR2 activation has also shown potential in models of multiple sclerosis (MS) by promoting remyelination and reducing neuronal damage.

Cancer Therapy: TNFR2 is a complex target in cancer; while it supports the function of immunosuppressive Tregs in the tumor microenvironment, blocking it can also enhance anti-tumor immune responses and promote T-cell killing of tumor cells.

I lodged a question for 30 Sept about the Affimer IP, whether the diagnostics IP goes with Coris or notand whether Avacta has retained any, e.g. for use as diagnostics alongside pre|CISION.

Datroway (datopotamab deruxtecan) is used to treat advanced, unresectable, or metastatic HR-positive, HER2-negative breast cancer in adults who have previously received endocrine therapy and chemotherapy. It is also being investigated for use in other cancers, such as non-small cell lung cancer (NSCLC), and works as a targeted antibody-drug conjugate that binds to and destroys cancer cells expressing the TROP2 protein.

These are the side effects of Datroway (datopotamab deruxtecan):

More common

• Blurred vision

• burning, dry or itching eyes

• cough

• diarrhea

• discharge, excessive tearing

• dizziness

• dry eye

• eye redness, irritation, or pain

• facial swelling

• fever or chills

• headache

• loss of taste or smell

• muscle or body aches

• nausea or vomiting

• redness, pain, swelling of the eye, eyelid, or inner lining of eyelid

• skin rash

• stuffy or runny nose

• swelling or inflammation of the mouth

• trouble breathing

• unusual tiredness or weakness

• watering of the eyes

Less common

• Agitation

• anxiety

• bladder pain

• bloody or cloudy urine

• chest pain

• coma

• confusion

• cough

• decreased urine output

• depression

• difficult, burning, or painful urination

• fainting

• fast heartbeat

• frequent urge to urinate

• general feeling of discomfort or illness

• hostility

• irritability

• lethargy

• lower back or side pain

• muscle twitching

• rapid weight gain

• seizures

• stupor

• swelling of the face, ankles, or hands

• thickening of bronchial secretions

Rare

• Pale skin

• unusual bleeding or bruising

https://www.mayoclinic.org/drugs-supplements/datopotamab-deruxtecan-dlnk-intravenous-route/description/drg-80008469

Well not quite "sparing normal health tissue" (sic)... "having minimal effect on normal healthy tissue" would be more precise.

(...continued)

In one embodiment, the target small molecule is cortisol, vitamin B12, estradiol, testosterone, or 25-hydroxyvitamin D2 and/or D3.

In one embodiment, the second binding polypeptide is an antibody or fragment thereof (e.g. a monoclonal antibody or fragment thereof) or a naturally occurring polypeptide.

In one embodiment, the target small molecule is cortisol, estradiol, testosterone, or 25-hydroxyvitamin D2 and/or D3 and the second binding polypeptide is an antibody or fragment thereof (e.g. a monoclonal antibody or fragment thereof).

In one embodiment, the target small molecule is vitamin B12 and the second binding polypeptide is transcobalamin II, and the complex is holotranscobalamin.

In one embodiment, the recombinant first binding polypeptide comprises an amino acid sequence represented in formula (I):

NTB-HP1-CB-HP2-CTB"

(...continued)

Further obstacles arise when attempting to detect and/or quantify a target small molecule in a so-called ‘sandwich’ format. Most binders in such a complex will effectively cover all available epitopes on the target small molecule. Therefore, most assays rely on competition between the two binders for binding to the small molecule. That results in an indirect readout. In such assays, the readout depends on a decrease in signal that correlates with an increase in target analyte. However, such indirect readouts resulting from competitive binding of two binders to the same target analyte are inherently less specific and/or less sensitive. Importantly, a direct readout also provides a broader dynamic range and/or a reduced susceptibility to cross-reactive binding.

There is a need in the art for approaches to detect and/or quantify target small molecules by assays that produce a direct positive readout, i.e., in which an increase in signal directly correlates with an increase in target analyte.

SUMMARY OF THE INVENTION

The present invention provides recombinant (first) binding polypeptides (e.g., Affimer® polypeptides) and methods of using them to detect small molecule analytes in biological samples with high specificity and sensitivity. The recombinant first binding polypeptides of the invention bind specifically to a complex of a target small molecule with a different (second) binding polypeptide (e.g. an antibody or a naturally occurring binding protein) and, in doing so, can be used to specifically detect the target small molecule. Recombinant first binding polypeptides of the invention are capable of specifically detecting target small molecules with high sensitivity and specificity, including target small molecules having a molecular weight of 2 kDa or less.

Thus, the present invention provides reagents, means and methods for detecting a target small molecule (including those with molecular weights of 2 kDa or less) that avoid detection of cross-reactive, structurally similar non-target small molecules and/or that avoid detection of the second binding polypeptide not specifically bound to the target small molecule.

In one aspect, the present invention provides a recombinant first binding polypeptide that specifically binds to a complex of a second binding polypeptide and a target small molecule,

wherein the recombinant first binding polypeptide is a recombinantly engineered variant of cystatin polypeptide,

wherein the second binding polypeptide binds specifically to the target small molecule, and

wherein the target small molecule has a molecular weight of 2 kDa or less, optionally wherein the target small molecule is a steroid, an organic compound, a hormone, a hapten, a vitamin, a biogenic amine, an antibiotic, a mycotoxin, a cyanotoxin, a nitro compound, a nucleotide or an amino acid.

(continued...)