Optimism

To all those holders who are worn out and worn down by the endless downward spiral of Starpharma's share price (aren't we all!), I would like to share my thoughts, and optimism.

All in my very honest opinion, of course. Not investment advice.

I remain confident. Which is why I have increased my holdings by 25 % in the last couple of months. So cheap!

Why?

Because we have enough cash for the time being, and more coming, so I am not worried about a capital raise.

I am extremely relieved that Starpharma should not need to raise capital in such a bad environment, as many other tech/biotech companies have had to do in the difficult environment.

I believe Starpharma should receive sufficient cash to negate the need for a further raise, from:

• a new licence for vivagel BV to replace Mundipharma

• licencing deals for DEP Docetaxel, DEP Cabazitaxel, and DEP Irinotecan.
  

• Over $7 million R and D research rebate in early 2024.

Because our 3 phase 2 DEP chemo drugs hold tremendous promise, IMHO, and are likely much more valuable than what most people realise. (The same should apply to DEP Gemcitibine).

I am very confident that these drugs are very valuable and will be very attractive to Big Pharma for licencing.

For those who are not convinced there is much value in our DEP Chemo drugs, consider this:

Chemotherapy is still very widely used and is not going away anytime soon. Especially improved versions of chemo.

Some people have expressed concerns chemotherapy (including DEP chemotherapy) will be displaced by newer therapies.

This kind of risk is always present, of course, when investing in biotech but I am not concerned.

Even as newer cancer therapies emerge, cancers, due to their mutational nature, inevitably escape the therapy, resulting in trying the next line of treatment (if the patient is up for it). In other words, it is usually not the case of either X treatment or Y treatment, but X treatment, followed by Y treatment (first-line, second-line, etc). I have seen this in multiple patients who have received newer therapies. They have still been offered chemo after progression on a newer therapy. So, treatments are often not necessarily displaced but their order of use might change.

Chemotherapy remains indicated, and re-imbursed, first- line for many cancers. Where chemotherapy has been 'booted' further back - eg. to second or third- line - after other types of cancer therapies, it is still going to be used in most cancer patients IF the patient is thought to be fit enough to tolerate it, OR if they don't refuse it (because of the toxiticies of current chemotherapy agents).

It is likely true that traditional chemotherapy (due to its toxicity) will be gradually phased out / pushed back / displaced as better tolerated and/or more effective therapies emerge but the nature of chemotherapy, too, is changing for the better and, IMHO, will continue to play a major role in cancer therapy. More targeted, preferably safer, chemotherapy is where chemotherapy treatment is headed. This change is nothing for SPL holders to be worried about asTHIS IS EXACTLY THE AREA WHERE STARPHARMA'S TECHNOLOGY IS THE FRONT-RUNNER.

Antibody drug conjugates (ADCs) against cancer are emerging as safer and more effective than traditional chemotherapy. It should be noted that ADCs with toxic payloads are actually just an example of a more targeted form of chemo - using a targeting agent to enhance the cancer killing ability of chemo agents.

Existing ADCs, however, still have very significant off-target toxicities (only a tiny amount of the injected toxic payload is actually successfully targeted to the tumour). Starpharma's DEP technology promises significantly better ADCs - utilising both an ACTIVE targeting agent, PLUS the PASSIVE targeting of dendrimers, PLUS the greater payload of dendrimers, to further enhance the cancer killing ability of chemo agents, with reduced toxicity compared to traditional ADCs.

Starpharma's chemo DEP drug conjugates (DEP Docetaxel, DEP cabazitaxel, DEP irinotecan, DEP gemcitibine, and more likely to follow) may not have ACTIVE targeting agents (eg. antibody, nanobody) but their significant PASSIVE targeting (enhanced permeability and retention effect causing accumulation in tumours up to 70 times greater) makes them very promising for a wide range of cancers.

The vast majority of cancers (and many individual cancer cells, or regions, within a 'targetable' tumour- as most tumours are heterogenous with their target antigen expression) do not have a target antigen that current ADC targeting agents can target. PASSIVELY targeted chemotherapy will remain very useful / important.

Combination therapies for cancer are being used more and more, utilising combinations of agents (eg. chemo plus chemo, or chemo plus immunotherapy). More efficacious, safer chemo drugs look very attractive in this context.

So, there is still a huge market for chemotherapy agents, going forward.

Especially chemotherapy agents available that are more targeted, cause less side effects and are more efficacious than the current chemo agents...... Well, here comes DEP Chemotherapy - to fill that need!

Safer, more effective, chemotherapy could definitely result in a move up in the rankings in some indications (eg. moved from 2^nd line to 1^st line) depending on how it compares to the other therapies.

Safer, more effective, chemotherapy would also likely be offered to many more patients (older, sicker patients) by physicians and be more likely to be accepted by patients, increasing the market size, and earnings, considerably, compared with current agents.

Regarding the monetary value of our three phase 2 drugs, consider the competitive landscape:

Abraxane :

• albumin bound paclitaxel (A TAXANE)
  
• used in breast, lung and pancreatic cancers.
  
• It does have some superior properties/efficacy compared with original paclitaxel but still has very significant toxicities (eg. anaphylaxis, severe hypersensitivity reactions, severe myelosuppression) which makes it quite a rubbish drug, really, in comparison to the lower toxicity that DEP chemotherapy agents promise.
  
• like other chemotherapy drugs with significant toxicities, the toxicities limit the market size for the drug. Older/sicker people are not offered the drug (physician advice), or often refuse the drug. Many patients forgo chemo to avoid the side effects and I don't blame them.
• Although Starpharma has not progressed DEP paclitaxel through to the clinic (they made a DEP paclitaxel in preclinical work many years ago which they could proceed with it at some time, if warranted) to make it an obvious competitor for Abraxane, DEP Docetaxel and DEP cabazitaxel have shown 'encouraging efficacy signals' in the phase 2 trials against cancers for which Abraxane is currently indicated, with far less toxicity. I believe DEP Taxanes will likely compete directly with Abraxane in the future (especially in pancreatic cancer). With the promise of much less side effects and superior efficacy due to DEP tumour targeting.
  
• Abraxane earnt US 1.25 billion in sales in 2020 and 1.18 billion in 2021, with most income generated in the US. (It has earnt less amounts in subsequent years due to source manufacturing problems in 2022, followed by patent expiries in some regions).
  
• I am very confident / I predict that our DEP taxane/s could strongly out-compete Abraxane in the future in terms of both safety and efficacy in one or more indications and be offered to, and accepted by, more patients. Accordingly, DEP Taxanes hold great promise to capture a much larger market and have significantly higher earnings than Abraxane.
  

Jevtana:

• Cabazitaxel. (A TAXANE)
• Like other taxanes, including Abraxane and docetaxel, it has severe toxicities and black-box warnings, which makes it quite a rubbish drug, really, in comparison to the lower toxicity that DEP Cabazitaxel promises.
  
• Will be in direct competition with DEP Cabazitaxel.
  
• ONLY ONE INDICATION in the US (and, I think, elsewhere) - MCRPC. So, a limited, but very large, market.
  
• IT IS SECOND LINE AFTER FAILED DOCETAXEL THERAPY (yes, docetaxel, for those who say DEP Docetaxel will likely be of little value, or 'a dud', standard Docetaxel pops up all over the place, if you look at standard chemotherapy regimes for common cancers. It is still very commonly used which bodes well for the future market of DEP Docetaxel).
  
• Results that Starpharma has released to the market from the prostate cancer cohort clearly outline DEP Cabazitaxel's superior SAFETY (less toxicity) and very significant IMPROVED EFFICACY despite the patients being heavily pre-treated, including with prior taxanes, including plain cabazitaxel (to which the cancers had developed resistance - which means the DEP cabazitaxel overcame this prior resistance). 96% of these patients had had prior docetaxel and 20% had had prior cabazitaxel. See ESMO poster 2022 for details.
  
• Jevtana earnt 455 million Euro in 2021, with less since, with generics entering some markets.
• I am confident / I predict that DEP Cabazitaxel will strongly out-compete Jevtana and have a larger market (offered to older, sicker patients and used in additional cancer types ) and holds promise for very significantly higher earnings.

Docetaxel:

• A TAXANE
• Extremely widely used, in multiple cancer types, on its own and in combination therapies.
• Earnt US 3 billion in revenue in 2011 prior to coming off patent.
• Virtually famous for it toxicity! Many people are not offered, or decline, docetaxel because of toxicities, which makes it quite a rubbish drug, really, in comparison to the lower toxicity that DEP Docetaxel promises.
  
• From what we have been told, DEP Docetaxel should show the same benefits over standard docetaxel as has been demonstrated (and released) with DEP cabazitaxel over standard cabazitaxel, but likely with a much larger market size opportunity due to the very wide applications of docetaxel, as mentioned above.
• It is difficult to quantify the market size for DEP Docetaxel due to no in-patent drug to use as a comparitor but I would say it should be absolutely huge. Starpharma did choose docetaxel as its first DEP drug to take to the clinic for a reason!
• I am very confident that DEP Docetaxel could ultimately be indicated and re-imbursed in a wide range of cancers, and offered to a larger number of patients (including the older and sickest who could not tolerate ordinary docetaxel) due to significant advantages (greater efficacy and significantly lower toxicity) over ordinary docetaxel.
  

In summary, OUR DEP TAXANES ARE LOOKING WAY, WAY BETTER IN COMPARISON to Abraxane, Jevtana and Docetaxel. (Unless Starpharma has been exaggerating their benefits seen in the phase 2 trials, so far. I just cannot see how this could possibly be the case).

• They are promising to be much safer, with far fewer side effects. This reduced toxicity, if efficacies are confirmed, should result in a much larger market size (more patients offered the treatment and more accept it).
  
• They, so far, are promising to be much more efficacious. Greater efficacy should also translate into much larger market size than current taxanes.
• Greater efficacy and safety than other (non-taxane) treatments could also result in them out-competing other therapies (other chemo drugs, non-chemo drugs) for some indications and capturing further market share.
  
• The phase two trials have seen them trialled in a wider range of cancer types, promising possible much wider usage and a much larger market.
  

Onivyde:

• PEGylated liposomal irinotecan
• ONLY ONE INDICATION (pancreatic cancer) used second line ( with 5-fu and leucovorin) after progression after treatment with gemcitabine-based therapies (DEP Gemcitibine's future is likely very bright). The owner, Ipsen, is seeking approval to use - in combination - first line in the US (after FDA fast-track and a successful phase 3), and just recently got the nod for first line therapy in the Euro zone, which should significantly increase its earnings.
  
• hyped up to be 'targeted' but not really very targeted at all. Its benefit is mostly derived from it being more stealthy in the bloodstream due to the pegylated liposome, reducing early clearance from the body and premature conversion of irinotecan to the active ingredient, SN-38.
  
• STILL HAS VERY, VERY SIGNIFICANT SIDE EFFECTS (along the line of standard irinotecan). BLACK BOX warnings for severe neutropenia and severe diarrhoea, which makes it a truly rubbish drug, really, in comparison to the lower toxicity that DEP Irinotecan promises.
  
• Earnt around 160 million euros in 2022 and should, soon, be earning a lot more, with further approvals recently and pending.
  

Plain irinotecan:

• off patent
• extremely widely used in colorectal cancer in combination therapies eg. FOLFIRI regime
• Again, a rubbish drug in terms of safety, compared to what DEP Irinotecan promises.
  
• It is difficult to quantify the market size for an improved version of irinotecan (DEP Irinotecan) but it should be very, very large, especially if offered to a wider range of patients (a much larger market due to older and sicker patients being treated, due to reduced toxicity, and due to being used in a wider range of cancers)
  

STARPHARMA'S DEP IRINOTECAN:

• Actually is DEP SN-38, with the PEGylated dendrimer providing both stealth and tumour targeting.
  
• what we know is that clinicians have been very impressed with its EXTREMELY GOOD TOLERABILITY. Remarkably non-toxic!
  
• DEP targeting promises greater efficacy as well and Starpharma have stated this is being seen.
  
• We have been told that it has shown 'encouraging efficacy' against a wide range of heavily pre-treated, end-stage, difficult-to-treat cancers.
  
• Market size promises be enormous, with pancreatic cancer, bowel cancer, ovarian cancer and other cancers likely to be treated by DEP Irinotecan.
  
• Will directly compete with (I predict decimate) Onivyde and ordinary irinotecan and promises to have very significant superior efficacy and reduced toxicity, from what we have been told.
• We all eagerly wait for some results from the phase 2 trial to be released soon!

VIRALEZE:

I think antiviral nasal sprays have a tremendous future ahead of them AND, judging from preclinical results presented at RESPI-DART conference in 2022, viraleze is looking likely to be among the best, or the best, of them. Pending results of further studies, of course. I am looking forward to the UK trial results by the end of the year.

I think many, many millions of bottles of viraleze will be sold in coming years:

Retail sales, sold OTC in pharmacies.

Healthy people in the population wishing to use as prevention to avoid viral respiratory infections or at first onset of a cold/flu to lessen their severity. The public will need to be advertised to (I hope widely promoted) but it also should gain steady increase in market-share through word-of-mouth recommendations

Prescribed or advised by health professionals.

I personally believe that an antiviral nasal spray (preferably viraleze!) should be part of every asthmatic patient's Asthma Management Plan (if you are not familiar with asthma management plans - just google it and look at what a standard plan looks like currently). This is because viral respiratory illness is the most potent trigger for asthma exacerbations and resultant: severe episodes of asthma, need for steroid medications, emergency department presentations, missed school, missed work, hospital admission, deaths, etc.

I believe Viraleze could/should also, in the future, be included in: COPD management plans, Bronchiectasis management plans, Cystic Fibrosis and Heart failure management plans, immunosuppressed people's management plans. etc

Health professionals will prefer to prescribe/recommend the most effective therapy with the least possible toxicity. At this stage, Viraleze is the front-runner, IMHO.

Should be used in high-risk environments to reduce transmission and control outbreaks. Eg. nursing homes, hospitals, cruise ships, aeroplanes, etc

We don't have any earnings from any established nasal sprays in the market place to benchmark from, so the possible future earnings of viraleze is difficult to quantify. But, if what I believe turns out to be true, (especially regarding common usage in common chronic diseases) the earnings could be potentially enormous.