Chris Heminway, Exec-Chair at Time To ACT, explains why now is the right time for the Group to IPO. Watch the video here.
Https://avacta.com/precision/
pre|CISIONTM, pre|CISIONTM drug conjugate (PDC), pre|CISION+ Immuno-peptide drug conjugate, pre|CISIONTM ADC
Massive shift in focus - why ..?
https://www.biospace.com/article/adc-market-will-remain-hot-in-oncology-reaching-30b-by-2028-report/
$30bn to go for – are we going to be ‘disruptors’?
“The report calls the antibody-drug conjugate (ADC) market the “hottest real estate in oncology” that will continue to attract big pharma investment over the next few years. In 2023, ADC-focused M&A and partnership activity totaled almost $100 billion in total in 2023, more than three times the value of similar deals in 2022 and nine times more than in 2019, Evaluate said.
Among the recent big deals: Pfizer acquired Seagen for $43 billion, AbbVie invested over $10 billion in ImmunoGen and Merck committed $4 billion upfront, with a potential total of $22 billion, for a stake in three of Daiichi Sankyo’s ADCs.”
GLA
But no mention of Dx on the page footer.
Site being re-built around us for Tx.
GLA
Also, this page updated today …
https://avacta.com/careers-landing/about-avacta/
“The pre|CISION™ platform is a highly specific substrate for fibroblast activation protein (FAP) which is upregulated in most solid tumours compared with healthy tissues. The pre|CISIONTM platform harnesses this tumor specific protease to activate pre|CISIONTM peptide drug conjugates and pre|CISIONTM antibody/Affimer® drug conjugates in the tumor microenvironment, reducing systemic exposure and toxicity, allowing dosing to be optimised to deliver the best outcomes for patients.”
Is this new wording ...?
“and pre|CISIONTM antibody/Affimer® drug conjugates …”.
GLA
While we wait, also at AACR ...
Old friend (Matthew Vincent) and current collaborator (William Bachovchin, Tufts - originators of pre|CISION™ chemistry) busy at AACR …
https://www.abstractsonline.com/pp8/#!/20272/presentation/8125
1874 / 18 - Common vulnerabilities of stem cells along the Barrett's-dysplasia-adenocarcinoma sequence
M. Vincent, W. Bachovchin
https://www.abstractsonline.com/pp8/#!/20272/presentation/3394
4654 / 7 - Targeting poly-resistant stem cells in high-grade serous ovarian cancer via synthetic lethal drugs
M. Vincent, None, W. Bachovchin
https://www.abstractsonline.com/pp8/#!/20272/presentation/5474
6099 / 25 - Identification of intrinsic precursors of Barrett's and gastric intestinal metaplasia
W. Bachovchin, M. Vincent
Prof Banerji has a few other ‘engagements’ …
https://www.abstractsonline.com/pp8/#!/20272/presentation/4493
6221 / 24 - First-in-human study of acoustic cluster therapy consisting of PS101 combined with chemotherapy and insonation in patients with liver metastases of colorectal cancer origin
Presenter/Authors U. Banerji
https://www.abstractsonline.com/pp8/#!/20272/presentation/11454
CT111 / 19 - Pharmacokinetic and pharmacodynamic evaluation of NXP800, a novel GCN2 activator, in a first in human clinical trial
U. Banerji, The Institute of Cancer Research
https://www.abstractsonline.com/pp8/#!/20272/presentation/11411
CT035 - Proof-of-concept and preliminary efficacy of triple IAP blockade to maximize immunogenic cell death and induce efficient adaptive immune response: First report on the ASTEROID phase 1 trial
U. Banerji, Chugai Pharma
GLA
(Cmon Avacta, show off the science, demonstrate the safety and efficacy with great data, and do some deals)
This page updated today ...
https://avacta.com/therapeutics/
GLA
Was ‘ringing a bell’, so, on a little more checking …
https://avacta.com/wp-content/uploads/2021/04/Preliminary-Results-for-the-year-ending-31-December-2020.pdf
“Lead programmes include: AVA3996, a FAPα activated proteasome inhibitor; AVA7500, a FAPα activated platin; and AVA7000, a FAPα activated taxane. These are being developed in close collaboration with Professor William Bachovchin at Tuft’s University School of Medicine.”
From Wikipedia – “Platinum-based antineoplastic drugs (informally called platins) are chemotherapeutic agents used to treat cancer. Their active moieties are coordination complexes of platinum. These drugs are used to treat almost half of people receiving chemotherapy for cancer.”
From Google – “Taxanes include paclitaxel, docetaxel, cabazitaxel, and abraxane.”
So what is the sucrase 'angle'?
GLA
For both AVA-7000 and AVA-7500 - “Mechanism: sucrase stimulants”, “Active Indication: Neoplasms”.
Just one possibility ..?
https://pubmed.ncbi.nlm.nih.gov/7497836/
Good to see work still going with Tufts at the ‘Discovery’ end.
GLA
@O2, I suspect that there will be a ‘few [low] thousand’ retail investors like myself who have been here for a ‘few’ years and only ‘trickled’ (as opposed to ‘flooded’) ‘in and out’. Would guess said retail investors account for well over 50% of shareholdings.
Question is – are there due to be directors up for re-election at the next AGM (I believe a 3 year cycle)? Easier to register to vote at the AGM than organise for an EGM. Serious commercial mistakes have been made, so let’s see where this goes. (Underlying science brilliant and trial progress to date seems very good, though).
GLA
A lot to go at if FAP targeting is ‘cracked’’. I think that this doc is referenced in Avacta presentations (table page 802) …
https://jnm.snmjournals.org/content/jnumed/60/6/801.full.pdf
Recent (up-to-date research) find courtesy Marty McFly@Blueberrymgmnt from twiX …
https://twitter.com/Blueberrymgmnt/status/1769307829762969766
The actual article …
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1352615/full
“Introduction: Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.”
A lot to read and take in, but looks a massive endorsement of the likely utility of the overall pre|CISION™ platform. Note - “Roche-supported, early- and late-phase studies” (page 3).
“.. a consistent pattern emerged: head and neck, breast, lung, and esophageal tumors exhibited the highest FAP expression ..”. (New guy on the trial at MSK, Alan L Ho MD PhD, is a ‘Head and Neck Cancer’ specialist).
GLA
Just to add (from the AACR itinerary planner) …
G. Lahu, ThinkQ2 AG, Baar, Switzerland …
In-depth expertise in Pharmacokinetic (PK) and Pharmacodynamic (PD) analysis of ‘drug’ in the body and the effect of a particular concentration respectively.
So why would we need these guys I wonder?
https://pubmed.ncbi.nlm.nih.gov/9352388/
“The rationale for PK/PD-modelling is to link pharmacokinetics and pharmacodynamics in order to establish and evaluate dose-concentration-response relationships and subsequently describe and predict the effect-time courses resulting from a drug dose.”
What’s all this dosing stuff then, surely we’re not delivering more dox (even if it were to be targeted to the TME) than ‘standard’ (before the AE’s prevent ‘more’), or even ‘experimenting’ with lower (but still higher – than ‘standard’), but more frequent dosing, just because it might be more effective? If we were being so radical, then even Alan might take some advice?
GLA
Just to add (sorry, have previously posted some of this) regarding the challenges of RLT (RadioLigand Therapy). The radioisotopes used are not inert – you can’t turn radioactivity off (unlike AVA6000 where Doxorubicin is rendered inert until FAP triggered cleavage at the TME), so targeting is critical. Not to mention the supply-chain challenges of radioisotopes (like, it might help to have a nuclear waste facility or a small CERN next door).
Lily (Point) and Novartis favour 177Lu and 225Ac (maybe 161Tb). 177Lu is produced by Neutron bombardment of 176Lu, or 177Yb - which then decays to 177Lu. 177Lu has a half-life of 6.6 days, so not long to manufacture the Radioligand. 177Lu decays via beta emission (3 energy levels) and gamma (1 energy level). The beta decay is the treatment.
Most 225Ac came from the Oak Ridge National Laboratory from slowly decaying Thorium – but this source is running out. However, you can always batter 232Th with high-energy protons – just need that accelerator next door. 225Ac has a 10-day half-life and decays via alpha emission (high energy, but very short distance, so needs precise targeting). Could go on, but getting late.
So what did Lily get for their money (Point Biopharma – acquired for ~$1.4bn (~£1.1bn))?
PNT2002 – RLT PSMA target, phase 3, trial met end-point, but results not up to expectations.
PNT2003 – RLT SSTR target, phase 3, FDA accepted abbreviated new drug application (ANDA), ‘frequent grade 3 / 4 AEs’, only 180 days exclusivity.
PNT2004 – RLT FAP-α target, phase 1 (177Lu), pre-clinical (225Ac), PNT2001 – RLT PSMA target, pre-clinical, CanSEEK™ - (i.e. pre|CISION™ licenced for RLT), status unknown.
Point had a strong balance sheet arising from a licensing deal with Lantheus at end-2022 involving PNT2002 and PNT2003 (so presumably Lantheus continue with a significant stake?).
Point had no product sales.
Avacta – market value (on 351m shares @ 53p) = £186m
AVA6000 - FAP-α activated doxorubicin, phase 1, going well so far, planning for dose escalation / phase 2. Presenting results at AACR 2024 April 9.
AVA3996 - FAP-α activated proteasome inhibitor, planning for FDA IND and phase 1.
AVA028/032 – PD-L1 Affimer, research / pre-clinical.
AFX-001 – Immunomodulatory Affimer being progressed by AffyXell (JV Daewoong) to FDA IND.
Avacta now have cash funding into 2026, however there remains an outsanding £38.25m of CLN debt.
Avacta have product sales from the Dx div (Launch and Coris) expected to be EBITDA positive in H2/2024 and cash positive in 2025.
Qualitative assessment – Personally (DYOR) I think that Avacta’s pipeline / technology is much more valuable. RLT difficult (major supply-chain issues), whereas pre|CISION™ is a true ‘platfom’ technology. I would (‘qualitatively’) judge Avacta Tx value being at least, likely more than, that of the Point / Lily acquisition deal.
GLA
Waiting for …
The ‘vote’ results at 11:00am today – “The Resolution is a special resolution to grant the directors of the Company authority to allot up to 37,479,124 New Shares (being an amount equal to the Conditional Placing Shares and the maximum number of REX Offer Shares) …”.
TR1’s and shareholder register update – who are the new II’s? The European fund, any US investors, did Conifer / BG take any more, etc.?
The ‘Significant Newsflow’ …
AVA6000 – AACR poster presentation 9 April, full ‘read-out’ of 2 and 3-weekly dose escalation study in late Q2, RP2D and commencement of phase 2 in Q3 2024,
AVA3996 – IND/CTA submission by Q1/2025 and phase 1a commencement in H1 2025,
Other pre|CISION™ platform pre-clinical pipeline updates,
Tx Affimers (inc. partner programmes – LG Chem, AffyXell),
Any hint of licensing deals or even acquisition?
Dx strategy / CLN resolution.
Etc.
GLA
Billiant find courtesy Marty McFly@Blueberrymgmnt from twiX …
https://twitter.com/Blueberrymgmnt/status/1769307829762969766
The actual article …
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1352615/full
“Introduction: Fibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.”
A lot to read and take in, but looks like a massive endorsement of the likely utility of the overall pre|CISION™ platform.
“Roche-supported, early- and late-phase studies” (page 3).
“.. a consistent pattern emerged: head and neck, breast, lung, and esophageal tumors exhibited the highest FAP expression ..”. (New guy on the trial at MSK, Alan L Ho MD PhD, is a ‘Head and Neck Cancer’ specialist).
GLA
AACR 2024 – “April 5, 2024: Text of Late-Breaking and Clinical Trial Abstracts Posted to Online Itinerary Planner (3 p.m. ET)”. i.e. in the public domain Friday 5 April pm.
So would expect the poster to be published by Avacta RNS / website update on either Friday 5 April (maybe after close) or Monday 8 April.
(But who knows as this relates to 'timings'?).
GLA
There does seem to be a clear ‘ethical‘dillema’ with AVA6000.
From what we know so far, pre|CISIONTM delivers AVA6000 to the TME where it is cleaved by FAP and dox is ‘dropped’.
Now ‘dox is dox’ and Dr Tap suggests that ‘a doxorubicin better than ‘standard doxorubicin’ (i.e. AVA6000) overnight becomes ‘the standard of care’.
So long as the ‘leaving group’ (pre|CISIONTM left overs) just leaves cleanly, then why would anyone want to continue with standard dox?
This is, surely, where trial designs / rules / protocols / etc. need to be flexible and we will no doubt be engaged with the regulators on the ‘fast track’ options.
However, the real solution is to put AVA6000 into the hands of an appropriate BP with the resources to deliver the therapy to patients in the shortest feasible timescale. Licensing or acquisition is the sensible (and ethical, for patients) path forward.
Let’s see what is revealed at AACR and also if we really do have any new US investors.
GLA
Agree that it is disappointing that there are (seemingly?) no UK hospitals with C7 or Q2W patients.
However, it is nevertheless encouraging that Professor Udai Banerji is taking the lead for us on the upcoming AACR poster presentation. I would hope and expect that he would be properly updated in advance, independently of Avacta, by at least one of Dr Tap and Dr Kranmer (MSK and Fred Hutch respectively).
Prof Banerji is still actively engaged in clinical trials …
https://www.royalmarsden.nhs.uk/our-consultants-units-and-wards/consultant-directory/professor-udai-banerji
But cast your minds back to the first patient dosed with AVA6000 …
https://www.lse.co.uk/rns/AVCT/first-patient-dosed-in-ava6000-phase-1-trial-mvh7gownm99pq9f.html
“AVA6000 Principal Investigator Professor Udai Banerji, Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust commented:
"I am delighted that the first patient has now received AVA6000 in the first-in-human study. This drug harnesses our understanding of the tumour microenvironment to enhance drug delivery - targeting potent anticancer therapies to tumours and potentially sparing patients debilitating side effects. It is fantastic that efforts are being made to discover and develop smarter, kinder treatments."”.
Good to see Prof Banerji is still with us.
GLA
WithPower trial recruitment site updated to ‘Breast Cancer’ in last day or 2 (could just be automated rotation through indications?) …
https://www.withpower.com/trial/phase-1-sarcoma-6-2021-6f477
Near-term news – ‘the vote’ (for additional new shares) on Mar 18, new shares released 19-26 Mar, another few weeks of ‘churn’ up to 5 April when “Phase 1 trial of the peptide drug conjugate, AVA6000 …” is revealed, followed by the actual poster presentation with Prof Udai Banerji on 9 April. Remember this from ~18 months ago …?
https://twitter.com/avacta/status/1575068600876269569
Other near-term news due (?) – Affimers, AffyXell, LG Chem, Dx, results notice, etc.?
GLA
Just to get this one ‘parked’ for now …
Aptamer Group (APTA) develop Optimers for diagnostic reagents and pharmaceutical solutions. Optimers specifically, as opposed to Aptamers more generally, are alternatives to antibodies but based on DNA or RNA oligonucleotide molecules (whereas Affimers are based on human stefin).
From an APTA RNS last year …
“We have made great progress in building a body of data further supporting our Optimer-based pharmaceuticals for gene therapy delivery and precision chemotherapy. This opens opportunities for the specific delivery of chemotherapeutics to site of action; for example, using these techniques to target specific tumours could reduce the amount of drug administered and thereby minimise side effects. We have successfully built the drug conjugates for oligonucleotide, radionuclide, and chemotherapeutic delivery, with the results showing selective delivery and gene knockdown or cell killing, respectively. This work will form the bedrock of technical data to attract larger pharmaceutical partners. Results from this work will be disseminated, as delivered, over the next 12 months.”
However, I would suggest that they are at least 3 years behind AVCT, even if they can get any funding.
From the Unilever RNS, what is somewhat interesting though (?), is the prospect of Optimers in food. This paper may be relevant in helping understand the background to what’s going on here (but please DYOR) …?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722326/#:~:text=The%20DNA%20oligonucleotides%20are%20intended,in%20the%20final%20food%20product.
‘Synthesised’ DNA in human food? Hmmm, not sure about that?
GLA
@jt, as per 54, approval (GM 18 Mar) needed for additional placing and retail shares.
Obviously, the whole additional shares / approval 'thing' would not have been required if placing done in good time at sensible price and without the appalling 'leaks'. Let's see if any consequences of Alan's demonstrable lack of commercial competence.
In the meantime, looking forward to some great trial results and further news on the pipeline and partners, not to mention Dx strategy and sorting the CLN.
GLA
29 Feb. “In light of the strong demand received both from existing investors and potential new holders, the Board has decided to increase the size of the Placing from approximately £20 million to £25.7 million.”
“27,390,485 Firm Placing Shares and 130,000 Direct Subscription Shares … will become effective at or around 8.00 a.m. on 4 March 2024 … not later than 8.00 a.m. on 11 March 2024”.
5 Mar. “The REX Offer … received total applications in excess of this [£6.8m] amount ….Avacta … only to allocate REX Offer Shares to existing Avacta retail shareholders and therefore a total of approximately £5.4 million (equating to 10,896,948 REX Offer Shares)”.
“Conditional Placing Shares and such number of REX Offer Shares as are subscribed for will become effective at or around 8.00 a.m. on 19 March 2024 or such later time and date (being not later than 8.00 a.m. on 26 March 2024)”.
So 27.5m shares placed already, or at least by Monday. Another 34.8m, subject to approval on 18 Mar, will hit the market from 19 to 26 March.
Just in time for … “updated clinical data from the First-in-Human Phase 1 trial of the peptide drug conjugate, AVA6000 will be presented at the 2024 American Association for Cancer Research (AACR) …”. Poster Presentation on April 9 (revealed on April 5). Expect Prof Udai Banerji (Royal Marsden, ICR London) will want to be associated with positive results.
Expect (DYOR) continued strong buying and sp recovery.
GLA