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If dox is released in the TME, why aren’t all tumours shrinking?
- Baseline characteristics of patients in the trial include that they have a median three lines of prior therapy; a large number on the trial can be considered chemo refractory. Criteria has been updated in the change of trial protocol. This remains a P1 trial and patients will sometimes have prior therapy. Patients without prior therapy can now be enrolled, for 2 week trial
Are any patients still receiving AVA6000 from C4/5/6, so have PFS of 6 months plus?
- 13 patients ongoing, 4 patients enrolled in C7, so 9 from previous cohorts. Evidence of disease stabilisation. In the first half of 2024 we plan an update of the clinical data and we will provide more info from the 2 weeks study.
Closing comments from AS - huge opportunities ahead, we are just at beginning of value curve, a lot to look forward to in 2024
Data seems to show AVA6000 is considerably safer - how is the patient experience and quality of life?
- Data showed significant reduction in severe toxicities, which led to improvement in patient experience, not only in quality of life but also length of time they can be treated. Safer drug over longer duration that is effective is the ideal scenario. This is optimal as we are able to stabilise the disease for even longer. Not shown in presentation, but we have analysed the mild to moderate toxicities which affect patient experience. Cellular damage is key to negative side effects including nausea and vomiting for example, in additional to mouth sores and lack of appetite resulting in major weight loss. These are reduced with AVA6000, as well as reduction of pain in muscles and joints. We do see reduction in AEs everywhere from Grade 1 - Grade 4.
65% tumour reduction - is this a good result? Would it have been matched with dox?
- It is possible that we’d see a similar response with dox, as dox is active in STS. Lowest response rate CC has ever seen is 6.4%, can get up into the 20s but response rate is very variable. What differentiates AVA6000 from standard dox is the observed time on treatment, as we saw in the patient case studies. Patient with 65% reduction has been on treatment nearly 10 months, duration of response is around 6 months and ongoing. Patient has a very similar safety profile to other patients in study, i.e. limited toxicity, “great quality of life”. Dox is limited to 6 cycles/18 weeks due to cumulative dosage limits, so the benefit we have with AVA6000 is not just tumour shrinkage, but they are shrinking and staying in shrunken state, so disease is stabilised for a longer time than can be achieved with standard dox
Is the plan still to retain complete ownership of AVA6000 or would you consider licensing for specific indications or territories?
- Plan is to retain AVA6000 for the foreseeable future and take it into P2. Strategically important to retain lead asset and build clinical pipeline, but also to accelerate the pace with which we can get drugs to patients. Can't do it all ourselves, will be a combination of partnerships and deals. We are in a fortunate position of having a platform which is clearly doing what it is supposed to do. Partner the platform, rather than lead asset. Both aspects are a very important part of our strategy
Why is C-Max so important in PK data?
- Dox is broken down into a number of known metabolites, one of these is called doxorubicinol, which causes formation of free radicals which then causes cardio damage. C-Max of dox drives this cardiotoxicity; reducing C-Max as AVA6000 does is going to have a significant impact on safety profile, but crucially doesn’t limit the efficacy of the drug - an important distinction to make
- bone metastases observed later, however, so classified as mixed response - this is a typical progression of solid tumours and this type of sarcoma.
- Tumour shrinkage still observed in this patient; good demonstration of AVA6000 action
- Three SFT patients, treated at between 200 and 250 mg/m2 - all three have prolonged stable disease, importantly across multiple patients, no progression over 4 - 8 months of therapy (in contrast to max 4.5 months allowable on dox)
- Favourable PK profile of AVA6000 means patients can continue to receive more cycles
- Outcome overall is more cycles and higher doses
Alastair
- Data 'unequivocally” shows AVA6000 is specifically releasing active dox in TME
- Targeting of active drug to TME has significantly improved safety and tolerability of dox
- Efficacy signals are very encouraging
- Two weekly study upcoming to optimise dosing schedule and further clinical development, US patients currently being screened
- P2 on track to begin in 2024
- Look forward to keeping investors updated
Questions
Why does Precision modification prevent chemo entering cells? What is the mechanism?
- Change in polarity of molecule, a lot of work done in chemistry teams to design substrate in the right way
Why were these dose levels chosen for two-week study?
- The starting dose for the three weekly study based on observations in preclinical study. Three weekly data supports ability to intensify dosing of AVA6000 in 2 weekly study - safety and tolerability data considered, including over the long term, plus PK data in terms of distribution in the body/TME, also considering preliminary efficacy signals from study so far. 160mg dose level chosen as this is where we first saw signs of efficacy, and was also the dose level where we saw the first instance of a Grade 3 or 4 AE, so a very favourable safety profile. Data allows us to extend treatment time from around 4 months with standard dox to up to 15 months in the case study example
Generic versions of various chemos - what is the market size? If this is not the preferred option for Avacta then why?
- Best way to maximise shareholder value is to develop the most effective drugs possible, some may involve generic chemos but pharma has moved on in the last decade - there are other cytotoxin examples that are too toxic to be used alone. It makes most sense to choose the most potent cytotoxics than just choose generic chemos, but likely to be a combo
Great to listen to the update just now - the case studies and improvement in the patient experience sound amazing.
I made some notes as I was listening, please add anything I missed or noted down incorrectly. I didn't make many as many notes during the main presentation as a lot of it was known information or covered in the content of the slides that have been released.
Fiona
- Precision concept is that the chemo drug remains inactive until it reaches the tumour TME
- AVA6000 is not cell permeable so remains inert in body until it reaches tumour and is cleaved
- Data supports the above hypothesis, and that the Precision peptide is ‘exquisitely selective’ for FAP
- AVA6K is only cleaved by FAP and not other enzymes
- In vivo studies in mice used cells from sarcoma patient xenografted onto animals - significant tumour volume reduction shown for AVA6000 versus straight dox
- High FAP tumours show stronger response to AVA6000
- Clearly able to administer higher doses of AVA 6000, which delivers dox directly to TME
P1 clinical data - Christina
- AVA6000 cannot enter cells intact so cannot cause same systemic damage as dox
- Only cleaved by FAP located in TME so highly specific to tumours
- Given specificity, we should see greater anti-tumour activity in high FAP tumour patients
- Median age of patients is 65, all aged between 30 - 79
- 85% of patients are white, 63% are male
- 12 patients with STS, 11 colorectal, 8 pancreatic, 9 other
- Cohorts 5, 6 and 7 all have patients with ongoing treatment
- Minimal serious AEs observed in all cohorts - no Grade 4s in C6 or C7
- 13 patients currently receiving ongoing treatment on trial, data still maturing and being collected
- 59 year old STS patient treated at 160mg/m2, originally expected to have limited response but actually had deepening response observed, with a 65% reduction in tumour volume from its baseline measure
- Over time the response has continued to increase for this patient
- Duration of his response is more than 6 months, patient is approaching 10 months on trial and is “doing well”
- Straight dox can only be administered for 18 weeks; however, due to the limited bloodstream exposure in this patient and others, we’re able to dose the patient with an additional 7 cycles if the tumour continues to not progress - this will result in a total of 15 months on AVA6000 therapy
- This is almost 3 times the length of time of the treatment if the patient was on standard dox
- Tumour biopsy from this patient has high FAP expression - supporting hypothesis that high FAP tumours/patients more responsive to AVA 6000
- Female patient aged 79 also has STS, and has been treated at 250mg - achieved a minor response at the time of the first scan, but the response deepened at second scan, going from 14% to 22% reduction
Cut off from the post above - "we want to get off to the races"
Moving towards Nasdaq more rapidly - any timeline?
- can't say when but it is ambition or any biotech that wants to grow rapidly. Nasdaq on agenda but no timeline as yet, have to be careful with specifics
Multiple partners on the cards?
- yes, very BD focused, always discussing with pharma, just got back from event in Europe where discussions were had - many ways we could structure a mutually beneficial deal
What other uses/disease types for POLB001?
- acute inflammatory conditions, IP attorneys advise not to be specific about diseases as it will create competition and may affect future patent filings. Delighted with data from completed challenge studies. Pharma like looking for drugs that have multiple uses, we believe POLB001 could be attractive in that sense
Impact of POLB001 as therapy for CRS?
- new immunotherapies are game changing. Cancer physicians don't like to talk of cures but are now seeing remarkable efficacy in more modern drugs. CRS has big impact on hospital costs and occupancy for example so exciting in that regard how POLB001 could help here
Any immunotherapies that could complement POLB001?
- game changing therapies coming online, need to weigh risk/benefit profile but higher risks often acceptable in cancer setting (missed most of this question and answer unfortunately)
CF, as the largest shareholder in POLB and HVO, if you were going to buy more shares, which one would you choose?
- CF always follows his money, never sold a single share in HVO, hopefully one day may get acquired. JS doing fantastic job at POLB. Difficult as chairman to get a window to buy shares. CF would certainly like to buy more shares in POLB if a window becomes available.
- Strong interest from pharma in potential for POLB001 to increase market size for their oncology drugs
- ongoing discussions around potential partnerships, 'all about' commercial aspect now at POLB
- AI programmes - exciting, very large datasets available from human challenge trials
- 'Terrific' collaboration with Cytoreason on influenza, aiming to identify novel targets - now moving on to lab based validation
- OneThree Bio collaboration focused on RSV data, excited about progression
- Oral delivery platforms - metabolic condition focus, diabetes, obesity etc
- Oral GLP-1 Agonist - avoids need for injection, proof of tech clinical trial planned for 2024 H1 - clinical trials expected to be short in duration but to generate highly valuable data
- GLP-1 Agonist market forecast to reach $150bn+ by 2031 - "market is huge, very exciting drug class"
- JS emphasised it's a platform rather than single drug, we can do numerous types of deals for 'whatever cargo' we want to deploy
- investment case - currently at nice inflection point, SP trajectory similar to Amryt is the objective
- enhanced leadership team, dual track business model, high value programmes with active partnership discussions underway
- POLBin strong financial position, cash balance £14m as of June
- cash position carefully controlled
- JS excited about where POLB is sitting right now, markets will be kept updated with upcoming newsflow
Questions
Licensing new drugs takes time - will you need additional cash before sales income starts?
- fortunate to be in a good cash position but things do take time. Careful to manage cash flow. A lot of distressed assets around including approved assets or close to approval; unfortunately as a result of pandemic and excessive cash burn, more distressed assets around - 'foot on the gas' when DA joins in December, want to move quickly in terms of deals
Are new employees full time and how do they fit?
- yes full time and some replacing existing staff
Comment on prospects for oral GLP-1 programme? Topical re: news from AZN this week.
- great to see deals in this space, validates and demonstrates appetite and interest from pharma for this type of product. Oral format makes compliance and convenience much easier. Short clinical trials to get data. Discussions with pharma so far show clear interest in the programme and product.
As POLB moves to new business model - focus on licensing? (missed rest of question)
- POLB will be opportunistic, we have evolved signficantly already in terms of programme scope and opportunity. Team in place to execute on strategy. Goal is to look for approved/pre-approval/clinical assets to progress with. If a disease has clear unmet need and an asset has value proposition to solve that need better than current options, we can be stewards of the asset to get it to patients at appropriate price. Unlikely to take on big P3 programme with big lag/clinical risk - "we want to ge
Great presentation just now in my opinion, all presenters sounding very upbeat about prospects for POLB.
Made some notes as I was listening, it was hard to keep up at times so please add anything I missed if you caught it:
Presentation
- CF "only appears when there's something exceptional and today is one of those days"
- CF has successfully IPO'd four companies
- POLB is about to pivot and replicate success of Amryt
- Amryt team joining POLB in Dec/Jan, aiming to create billion dollar mcap company
- DA - encouraging to see SP reaction to new team additions; 30 year background in pharma, inc. 9 years in Amgem while it was in its ascendancy, great learning ground at a growth company
- DA approached by Celgene at an early stage of the company, major role in building company up, various leadership roles while at the company
- Later joined Amryt as fourth or fifth employee, remit to drive growth across region
- Opportunity at POLB is the great R&D program, 'find a beachhead, get going, build momentum/revenue' - once team and capability has grown we can drop in additional assets to leverage that expertise
- Looking forward to keeping SH informed of news in coming weeks and months
- JMc (CLO) instrumental in getting Amryt on Nasdaq
- DA replacing David English
- Laura Maher replacing current clinical ops exec
- will be hearing more about 'dual track approach' in coming weeks and months for POLB, replicating strategy of Amryt, 'proven to create shareholder value'
- POLB 'getting close to having real revenues and a pathway to profits'
- HVO and Venn never made money, now profitable since Open Orphan
- JS - very exciting time for POLB, now very well positioned for success, terrific new hires, great fit for the company
- dual track very important, mindful of keeping costs low
- oncology angle of POLB very well received so far, also excited about outputs from AI collaborations
- good position to push all three programs forward, strong financial position too
- robust pipeline generating data that is attractive to potential partners
- POLB001 - clinical stage, proven safe and well tolerated, excellent data from trials so far
- pharmas like to see in-human data
- strong patent portfolio, protection til 2038
- 'statistically significant reduction of TNF-a' in POLB001 human challenge trial, safe and well tolerated across all doses
- TNF-a is only one example of positive effects, also seeing impact on other aspects of cytokine storm (missed the names)
- POLB001 data to be presented at ASH meeting in San Diego next month; 25000 haematologists and other professionals attending, organisers 'see potential' in POLB001 so happy to be accepted to present the data
- Excited for POLB to be branching out more widely
- One dosage level of AVA6000 to be taken forward if key thresholds are met, to a randomised P2 trial where focus would be efficacy rather than safety and tolerability
- Market potential for AVA6000 beyond STS include breast cancer, ovarian cancer, Hodgkin and non-Hodgkin lymphoma, and combinations of therapies
- Large unmet clinical need for STS to improve patient outcomes in difficult to treat tumours
- dox is a “stubborn standard of care agent that everyone is hoping to replace” due to limited clinical benefit
Questions
Phillipa from Trinity Delta - raised liver enzymes - any comment on why appearing but not for dox itself?
- Because data includes AEs that are both related and unrelated to AVA6000, raised liver enzymes are not related to AVA6000 treatment, and AVA6000 patients are heavily pre-treated compared to patients in the control arm who are much earlier on in their treatment journey.
Chris from Unicorn asset management - as dox has been around a long time, its efficacy is well understood - assuming your dose escalation phase continues to be positive, when you move into period where you’re testing efficacy, what risks are there that it would be less efficacious than existing standard dox treatments?
- Essentially we don’t know, we’re seeing proof of concept here, missing bit is proof of efficacy but we’ve included patients where anthracyclines is not standard of care - this proof will come in later parts of the trial, and that’s where we can compare AVA6000 efficacy vs standard dox. So, no particular reason why it could be less efficacious but this is the nature of clinical development - we need to put it to the test, potential for many unknown hurdles
From biopsy data - dox in the TME but is this active dox having been cleaved off from the substrate?
- Depends what you mean by “active”, i.e. is it resulting in efficacy and tumour shrinkage? We are including patients where anthracyclines is not typical treatment for their type of tumour. We need to move to more targeted patient population to assess this.
Nobody’s talked about MTD yet - are you close to it and is it important for optimal dosing and regulatory approvals?
- Not believed to be close to MTD, potential for substantial dose escalation. It would be a mistake to fall short if there were higher dose levels we could explore. “We are nowhere near MTD”, we’d usually need to have two DLTs in a cohort and we’ve only had one DLT across all cohorts, the drug has been “remarkably tolerable” so far
What would you typically expect in terms of FAP expression in biopsies?
- We don’t require patients to be FAP positive to join study, we have list of 12 tumour types that are known broadly to be FAP positive, we will look back retrospectively which of 19 patietns are FAP positive or negative and data to be released in due course. Good likelihood that patients are FAP positive
- Safety profile is “broadly modest”, and predictable, meaning largely seeing adverse events/toxicities that were grade 1 or 2 such as nausea, fatigue and decreased appetite
- PK data is key part of the program - shows that systemic levels of dox are “considerably lower” than standard dox
- Potential for many cycles of AVA6000, well above cycles of standard dox that is limited by cardiotoxicity
- Biopsies not mandatory but 6 biopsies completed
- Patients largely caucasian aged 50s/60s
- Tumour types include colorectal, pancreatic, ovarian, STS and oesophageal, mainly tumour types where anthracyclines not expected to offer clinical benefit, tumour types where dox is not part of standard care, apart from ovarian/STS patients - important in terms of tempering expectations around efficacy where anthracyclines are not currently used as standard of care. Patients are also heavily pretreated, median of three prior lines of therapy but up to 8, before receiving AVA6000
- Primary endpoint is safety and tolerability at this stage, not looking at efficacy
- Two patients had grade 3 related adverse events
- proportion of patients experiencing AEs is very low and severity of AEs is generally mild
- One DLT in 120mg cohort - heart failure but patient had significant risk for cardiovascular disease with diabetes and other conditions - on expert cardiology review, DLT was judged *unlikely to be related to trial* - as doses have been increased beyond this cohort, similar DLTs have not been observed
- “Benign safety profile with little or no classic anthracycline related toxicities to date”
- Tumour biopsies taken 24 hours after day 1 AVA6000 administration - dox levels within therapeutic window where we might expect efficacy or clinical benefit
- Dox ratio biopsy:plasma variable but up to a ratio of 125:1
- “We are seeing very clear preferential concentration of dox released from AVA6000 in the tumour, relative to the periphery and is consistent with PK and AE profile that is emerging - a very consistent data set”
- Next steps after P1a - Soft Tissue Sarcoma is poorly served in terms of treatments, typical response rate is between 14% and 18% - most patients do not respond, some do achieve stability of disease, but there is huge room for improvement and also reducing typical risk of cardiotoxicity of standard dox
- More dox delivered at tumour means potential for many more than six cycles of treatment
- Patients with metastatic disease with FAP positive tumours in P1b, likely to evaluate two doses of same schedule of AVA6000, potential to enroll 24 patients in each schedule with a higher and lower dose in each
- In parallel, 12 patients receiving standard dox for six cycles to provide a comparison, with biopsies taken across all three groups
Questions
Protease targeted therapies have failed in the past, what makes Avacta’s different?
Difficult to get the selectivity right, without selectivity you get systemic release which is undesirable. Precision gets around this and will have proof in P1 trial.
ADCs - how does Precision compare?
- Similar strategy in terms of delivering toxic payload directly to tumour, but Precision prodrugs don’t need the tumour antigen targeting that ADCs need because we use FAP, so pro drugs are cleaved outside the TME and then taken up
Max Hermann from Stifel - second Precision molecule Velcade - variety of indications that are different to original Velcade; is pro version more broadly applicable because of therapeutic window, or suitable for myeloma for example?
- Myeloma not very high in FAP, Avacta is targeting high FAP tumours - limitation of Velcade is its toxicity so very interested in data that supports tumour agnostic approach
Chris, oncologist - Velcade showed activity in other tumour types but not sufficient to continue clinical development.
- We have three tumour types in which we are seeing a response, tumours are high in FAP, more studies ongoing and more data to come in AACR
Paul Hill - AVA6000 data, when cleavage happens and dox is deposited on tumour, confirmed by 6 biopsies, did we also see waste leaving come through in urine?
- Yes, measuring that now, not in current slide deck but urine collected up to 72 hours. Full data still to be correlated so we have full picture but currently mechanism of cleaving is confirmed by urine samples, but urine is not as robust a measurement as plasma, but has been useful info to gather
Follow up question - is the study so far confirming what you expected from pre clinical?
- That’s right
High FAP tumours - does this restrict number of tumours available for targeting?
- Some tumours have high FAP, some don’t, FAP levels can vary over time. FAP field is “on fire right now”, a lot of work in this area, including theranostics, imaging, lots of data in the public domain. Not every tumour is high FAP but that makes treatment more precise rather than limiting number of targets.
Comment from audience - this drug does appear to be doing what it is supposed to - no guarantee but it does seem to be derisked
Andrew Saunders
- Dox is successful chemo but has huge room for improvement, limited by risks, particularly that of cardiotoxicity
- Cohort 5 and 6 dosage still TBC, continuing to dose escalate in classic 3+3 design
- “Classic P1a dose escalation trial”, patients enrolled with end stage solid tumours, metastatic disease, heavily pretreated, typically very limited survival and no further treatment options
- 19 patients enrolled so far, across several common tumour types
- Patient population typically has two cycles of AVA6000 but have had patients with up to 8 cycles
Made some notes as I've been watching the Science Day recording - haven't managed to get through the whole thing yet but there's some fantastic detail in what I've watched so far. I have to admit Dr Komanduri's presentation went way over my head so I didn't make many notes there, and I may have missed some details elsewhere so feel free to add anything I missed or correct anything I got wrong.
Intro from Alastair
- In a very fortunate position as a biotech to have two proprietary platforms
- “We are at a very exciting stage in our development with an *unparalleled* opportunity to develop really meaningful new cancer therapies“
- Very confident that Avacta will play a major role in the revolution of cancer care over the coming years
- Particularly excited about and proud of the fact that the Precision pipeline is not only more efficacious but more affordable - important to the company that the drugs are widely available
Fiona McLaughlin
- Precision pro-drugs have no need for receptor mediated internalisation, a major advantage over ADCs
- “Exactly” dox is released, not a modified version, so we can use existing data for dox, which smooths development planning and regulatory pathway
- AVA6000 ‘markedly reduces tumour growth’ over time - heavily pretreated sarcoma patient
- AVA3996 ‘delivers proteasome inhibitor directly to the TME’
- Currently in IND enabling studies, first-in-human P1 trial planned for 2024
- Precision platform being developed in house, all knowledge kept within team
- AVA3996 ‘flat lines tumour growth without weight loss’ - body weight loss is a marker of toxicity; Velcade treated animals experienced significant weight loss and had to have a dosing holiday
- Precision-targeted Velcade has improved therapeutic index
- Data to be presented at AACR in April 2023 - more data than presented at Science Day
- ‘Difficult to drug’ targets such as GPCRs are focus for Affimer development work - smaller than antibodies for example, and more stable
- TMAC is combination of Affimer and Precision - warhead could be any cytotoxic payload; target is ‘first in class’ therapeutics
- Partnerships are fully funded and have potential to accelerate development of affimers
- Partnerships include Affyxell; AFX-001 showed superior efficacy in mouse acute GvHD model, and MoA has been confirmed in vitro and in vivo
- Affyxell data to be presented at ISCT Global conference in May 2023
- LG Chem is long standing partnership, PDL1 molecule currently in preclinical
- “Rich and diverse pipeline, multiple shots on goal”
Cytoreason - can AI capabilities be applied elsewhere - metabolic diseases as well as immune for example?
- Cytoreason look for clean clinical data which they can analyse and look deeply into immune responses. Pfizer also looking at this. POLB unsure about looking for entirely new metabolic disease targets; stick to the benefit we can derive from unique database and biobank - nobody else in the world has a database that dates back to just after WW2 that can be mined intelligently. We are opportunistically and potentially very valuably focusing on infectious diseases because of our heritage with challenge studies and the huge resources available to us in this area. We can also access other databases such as malaria model data - potential to collaborate with Cytoreason on other projects too.
Why no efficacy data in the RNS on Monday as promised?
- It will come as next step of program, initial data was just confirming safety. We were confident that the drug was safe but needed to confirm. Trials can be challenging but happy to confirm safety; efficacy to come next. Multiple doses were trialled so will get some insight into optimal dose from this.
Where can shareholders access info on clinical trial for POLB-001 - nothing on clinicaltrials.gov?
- Not a requirement to add the info for P1b, but we have to for P2 and P3. We are in discussions for adding it for public awareness - they do allow it for P1 and we are not trying to hide from it
Do you evisage POLB continuing to expand outside infectious disease or is this initiative a once off ?
- We are infectious disease focused, partner has interesting early human data. We are opportunistic when it comes to new opportunities
Have you patented POLB-001 for stopping cytokine storm during a Covid infection?
- Covid now is being well addressed, it's mutating but pharma and vaccines are pursuing this well - there are other areas where POLB could play a greater role
When POLB-001 is outlicensed, are we likely to get an upfront payment and if not when will we see first revenues?
- Upfront payment with downstream revenues is a standard model for this type of deal - we will pass asset to collaborator, they will run it and fund it, we get paid as they progress. From POLB's standpoint we have multiple shots on goal, POLB-001 is just one and the most advanced, but much else is going on in other programs
Are we already in discussions about reversing onto Nasdaq?
- CF mentioned recently we continue to look out for Nasdaq companies that could do with a cash injection, potentially with a pipeline of their own, "fallen angel" type companies, we continue to look for this and there is potential for POLB to end up on Nasdaq - good for fundraising, greeter liquidity, and sum of two companies could get bigger response from the market
Oral obesity delivery market?
Obesity is "frighteningly large" and a growing issue, tripled since 1975, global obesity sales in 2030 of $50bn+. Aiming to have role in
Made some notes on the webinar just now. It was mostly known information in the main presentation so I didn't note down everything there, but it was good to get an overview of how much POLB has achieved this year - worth watching the recording if you didn't catch it.
Main presentation
- Regarding multibillion deal between GSK / Affinax, "pharma doesn't mess around when it comes to doing deals... if they see something they like they will pay for it"
POLB-001
- no further clinical activity is required to complete objectives of the trial
- recruitment and clinical phase completed on schedule
- no serious adverse events reported
- POLB-001 is safe and well tolerated
- Data analysis has commenced, full readout expected Q2 2023
- Some expectation among some investors of having the data readout already; a lot of analysis currently ongoing, which is the next phase which demonstrates and proves the efficacy of the program
- Huge list of safety and tolerability endpoints, pharmacokinetic and pharmacodynamic endpoints - analysis will take time but is underway
- Blind nature of the study gives greater confidence in the trial data as it is analysed and revealed
- "excited to be at this stage... terrific achievement, delighted where we stand"
- Brendan Buckley now on scientific advisory board - former CMO at [highly acquisitive] ICON plc
- POLB is not attempting oral insulin, it's a "graveyard of capital" for the many who've attempted it
- Oral GLP-1 trial is not a phase 1 or 2, it's a "proof of principle" trial to determine that micro/nano encapsulation tech can safely delivery GLP-1 orally in humans
- Planning has already commenced on this, trial will commence early in 2023, "in a month or so"
- GLP-1 agonists for diabetes/obesity are a large and fast-growing opportunity/industry - estimated to be $22bn pa by 2025
- oral delivery significant health/cost benefits over injection
- cash balance £18.9m as of 30th June 2022
Questions
Which of POLB's plans for 23 are you most excited about?
- tough choice but will mention readout from POLB-001 and partnering that will follow - it is exciting for any pharma to get into the clinic and get subsequent results. Second choice would be "groundbreaking" AI program and analysis that comes from that. POLB is doing the same work in 9 months for RSV analysis that took Hvivo sunstantially longer. Outputs will be groundbreaking for the company and potentially for the industry. $110m spent by Pfizer in same space and with Cytoreason, same partner than POLB has. Everything else in pipeline also has potential
The ones I checked were mostly dissolved companies. Aptuscan was bought by Avacta years ago, I'd guess the dissolved limited companies were also bought by Avacta and incorporated into the parent group.
Seems like a good time to revisit this answer AS gave to a question about funding back in April (i.e. with five months' less trial data than they now have):
Funding options for further trials of Precision platform? In best interest of shareholders? Minimal dilution?
“Very mindful of using non-dilutive funding routes”. A number of dilutive and non-dilutive options available. We have a long cash runway. Good AVA6000 data will create huge value across the pipeline, allowing us to think about non-dilutive partnerships. This route is more attractive to the company as well as shareholders, so we are aligned.
Number of vaccine candidates other than POLB-003 for melioidosis - any update?
- Melioidosis candidate is further along so focusing on that, also keen on e coli and cystic fibrosis as there is major unmet need there. Early stages but monitoring closely. Don’t want to move too early as we have other assets further ahead in terms of development
POLB-002 and POLB-003 - dates for clinical trials?
- POLB-002 came with a very large and impressive data set so plan to move forward as quickly as possible. POLB-003 is under an option so we can “get our arms around that”, GMP standards being sought to allow use in humans, process underway and we will update the market in due course
Big pharma or target pharma in the wings for POLB-001?
- Pharma wants data. They are aware of POLB and what we are doing but discussions will start “in earnest” towards the end of the year when we have data. New head of business development will be key here. Territorial rights a possibility.
How long does POLB have access to ORPH’s data, any plans to extend?
- 30 months from demerger, currently 13 months in so 17 months remaining. Option to extend if required. ORPH is running new challenge studies all the time so new data is often available. JS would like this data analysed, spoke to AI partner recently about potential to expand the scope.
Evotec mentioned previously; any UK competitors and what is POLB’s differentiator?
- None in the UK that JS is aware of. Evotec has been very successful and POLB is looking to follow similar path, Evotec’s market cap is in the 3-4bn range, we will have done very well if we can emulate that, we are focused on growing value and executing our strategy to deliver shareholder value
If a drug candidate for development is found in the AI programmes, would these take priority over existing assets under development?
- What took Hvivo many years we can do in just a few months, so there will be potential to bring in new programs. If there is a molecule for example that is ready for challenge studies we can consider that, but priority for POLB is always early in human clinical data to present to pharma. We are flexible in our approach, so reprioritisation is possible.