The great value of the DEP platform technology

For existing and new investors in Starpharma

I am looking forward to millions of nasal sprays being sold! The main reason I am invested in starpharma, however, is for the amazing DEP technology.

I originally wrote this summary for some friends, to explain what I believe to be the great value of the DEP technology.

All in my honest opinion and, as usual, do your own research. Not investment advice but to generate discussion. I welcome other peoples comments.

Regards

Gumnut

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DEP stands for 'dendrimer enhanced product'. It is a platform technology that Starpharma has developed and refined over a long period. Starpharma's extensive intellectual property (IP) surrounding the use of dendrimer's for enhancing drug properties and delivery is protected by patents covering many different possible uses. Globally, Starpharma virtually 'owns the space' of dendrimer drug delivery technology: a very, very exciting technology that can improve the efficacy and lessen the toxicity of many existing and future drugs.

In my honest opinion, the medium and long-term monetary value of the DEP IP and practical know-how that exclusively belongs to Starpharma is currently vastly underestimated by the market. When the current phase 2 trials of DEP chemotherapy agents are completed (later this year) and the 'proof of concept' is confirmed (very likely IMHO), I believe big pharmaceutical companies will strongly desire Starpharma's technology and be prepared to pay very high prices to partner and licence the technology, or perhaps attempt to buy Starpharma out at a very substantial premium.

SUMMARY OF BENEFITS OF DEP PLATFORM TECHNOLOGY:

Improved EFFICACY

Reduced TOXICITY

Extending the DURATION OF ACTIVITY of the drug in the body

TARGETED DELIVERY of drugs to organs, tissues or molecular receptors

Increased SOLUBILITY

Starpharma has applied this technology in its own development programs (such as DEP^® docetaxel) and in partnership with pharmaceutical companies including AstraZeneca, Merck and a number of other undisclosed partners. The technology has applicability for many different diseases.

DRUG-DELIVERY PLATFORM TECHNOLOGY:

A dendrimer is a multi-branched, roughly spherical, polymer nanoparticle. This is the ‘CARRIER’.

Pharmaceutical agents, such as a drug, radio-isotope, or antibody/antibody fragment (the ‘TOOLS’) can be attached, through chemical links, to the outside points of the 'star-shaped' molecule. (I like to visualise more of a multi-branched 'snow-flake' structure). Attachment to the dendrimer enhances the pharmaceutical qualities and properties of the active agent/s.

Around 70 percent of existing drugs could be attached to a dendrimer, if this was to be desired, demonstrating the versatility and possible widespread application of the DEP process. The drugs which are best suited (high-value), however, for DEP technology are drugs which have promising activity but their use is limited by off-target toxicity or by their pharmaceutical properties inside the body. Chemotherapy agents and targeted drug delivery (antibody-drug conjugates – ADCs) are particularly suited to DEP technology and are obvious 'high-value' targets, but other drug classes can also benefit as discussed below.

DESIGNER LINKAGES:

The nature of the chemical bonds or 'links' used to join a therapeutic agent (eg. a drug, antibody, radio-pharmaceutical or radio-diagnostic agent) to the dendrimer 'carrier' molecule can be manipulated depending on the desired property (eg. creating a moderately slow release, or very slowly release drug).

DESIGNER SIZE:

Starpharma can produce these dendrimers to a desired 'designer' size, which influences their properties in the body. For example, SPL7013, the dendrimer in VIRALEZE nasal spray is a designed large-sized dendrimer molecule that both jams up the spike proteins of multiple viruses, 'disabling' them and is also of a size that is too large to enter the body, ensuring it remains a surface-acting drug, when used topically. Another example of the benefit of a 'designer size' is the accumulation of DEP Docetaxel in tumours, discussed further below. This is due to its physico-chemical properties (physical size, as well as chemical properties such as solubility), resulting in a greater concentration (and effect) at the desired site. These same properties also limit entry into the bone marrow, reducing bone marrow toxicity.

SUPERIOR SOLUBILITY:

The dendrimers used for the DEP technology are highly water soluble. Poorly water-soluble drugs can be rendered more soluble and their pharmaceutical properties improved significantly. Examples are the many highly water-insoluble chemotherapy agents and some anti-infective drugs. Existing DEP versions of these classes of drugs include DEP Docetaxel, DEP Cabazitaxel, DEP Irinotecan and DEP Remdesivir.

An additional advantage of increased solubility is that the drug can be delivered in much smaller volumes. For example, small volumes such as 3-5 ml could be given subcutaneously at home or in the nursing home, instead of 300-500ml needing to be given by IV infusion over a longer period in a hospital. Many existing IV chemotherapy drugs also need co-administration of a detergent, due to low solubility, with associated increased side effects and toxicities. DEP versions of these drugs will not require this.

EXTENDED DURATION OF ACTIVITY:

Extended duration of activity may allow a drug to be delivered much less frequently. For example, 3-5 ml subcutaneously, once a week as an outpatient, instead of 500ml by IV infusion daily in a hospital.

IMPROVED AND MORE PRECISE DRUG DELIVERY = BETTER EFFICACY AND LESS TOXICITY:

Superior solubility and the ability to produce the desired (' designer') size of each of starpharma's dendrimers improves delivery to where they are most needed, improving efficacy and reducing toxicity. This has been impressively demonstrated with DEP docetaxel in preclinical studies and then in the patient case study released from the current phase 2 trial, where there was a63 times greater concentration found in the tumour biopsy than in the blood. BETTER EFFICACY can be achieved through improved delivery. Also reported from the phase two cancer trials has been less hair loss and bone marrow toxicity. LESS TOXICITY can also be achieved due to more targeted delivery to the tumour tissue.

NEW DRUGS:

Large pharmaceutical companies have already established partnerships with Starpharma to 'DEP' their drugs under development, because of these advantages. The best example of this is AZD-0466, Astrazenica's promising new chemotherapy drug under development. The original compound was found to be too toxic in pre-clinical trials to be taken any further. The DEP version, however, has much-reduced toxicity (resulting in a 26 times better therapeutic index) allowing the active agent to progress further into the clinic. AZD-0466 is currently in phase 1 trials and is looking very promising, with Astrazenica recently announcing a large expansion of the trial sites to speed up its development.

I believe that an increasing number of pharmaceutical companies will approach Starpharma topartner with them to develop new drugs in the future once the benefits of the DEP technology become more widely demonstrated and known.

OLD DRUGS RE-INVENTED. (NEW MOLECULE, NEW 'DRUG'):

Valuable existing drugs, whose patents have expired, or are soon to expire, can be attached to a dendrimer, thereby allowing the 'new drug' to have a NEW PATENT LIFE, as well as improved properties (greater efficacy and less toxicity) than the existing form of the drug. Starpharma’s chemotherapy pipeline includes DEP versions of existing, very important and widely used drugs, with expired patents. Starpharma also has an agreement with Astrazenica to 'DEP' an undisclosed existing high-value drug which is about to come off patent.

Applying DEP technology to existing valuable drugs, with proven track records (efficacy and established clinical usage), to produce new, improved versions (with BETTER EFFICACY and REDUCED TOXICITY) with a NEW PATENT LIFE appears (IMHO, DYOR) to be potentially the most valuable biotechnology concept I have ever come across (and I have done deep research on many, many biotechnology stocks). This is not only because of thevery large number of ‘off-the-shelf’ possible candidates that this platform technology could be applied too, but also thevery significant reduction of investment risk that is usually involved with investing in drugs under development:

1. That the agent may prove to be less EFFECTIVE in clinical trials than was suggested in preclinical studies.

Effectiveness and real-life success of the unimproved agent hasalready been demonstrated in clinical usage in the market before any improvements.

2. That the agent may have TOXICITY concerns when it reaches the clinic.

I am confident that the reduced toxicity of DEP drugs (compared to the active agents on their own) will be confirmed to be a reliably reproducible PLATFORM TECHNOLOGY EFFECT. One could then be confident that the new DEP version of any existing drug can be quite reliably predicted to be less toxic than the existing drug (which, in the case of old drugs, has already been found to be safe enough to reach clinical usagebefore any improvements).

DEP technology could potentially be applied to a VERY LARGE number of existing drugs with proven track records. I expect Starpharma will increasingly expand their pipeline of ‘internal DEP’ candidates as they grow and have access to greater capital. I also expect other drug companies to increasingly come knocking on Starpharma’s door asking to partner with them to develop DEP versions of OLD DRUGS and for development of their NEW DRUGS.

ADVANTAGES OF DEP CANCER DRUGS:

As discussed above, DEP technology is ideally suited to chemotherapy agents due to their inherent toxicity. DEP Docetaxel and AZD-0466 are good case studies that demonstrate the huge advantage that DEP technology can bring to chemotherapy drugs, resulting in BETTER EFFICACY through improved delivery and LESS TOXICITY due to more targeted delivery to the tumour tissue. These advantages have also been demonstrated in the other agents currently in phase 2 trials: DEP Irinotecan and DEP cabazitaxel.

Better efficacy and less toxicity could also mean a WIDER APPLICATION for an old cancer drug, or a greater possible target application for a new drug. For example, the phase 2 trial of Docetaxel has been expanded to cancer types not currently targeted by ordinary Docetaxel. (Docetaxel is one of the most commonly used cancer drugs. It is worth keeping in mind that Docetaxel, before its patent expired, earnt $3 billion dollars in revenue in 2011). I expect DEP Docetaxel to be found to be effective against a much wider suite of cancer types than ordinary docetaxel, as well as being more effective (with less side effects) against it's established 'target' cancer types. WIDER APPLICATION of such a drug should translate into much greater earnings than the original drug.

Starpharma has its own ‘internal’ pipeline of DEP chemotherapy drugs. It also has a multi-drug agreement with Astrazenica for collaborative ‘external’ development of further DEP chemotherapy agents. I expect many multiple further ‘internal’ and ‘external’ DEP chemotherapy candidates to emerge in the future.

ADVANTAGES OF DEP ANTI-INFECTIVES:

Improved solubility and greater control over the half-life of antivirals and antibacterial agents can be expected to improve the properties of these agents. The chemical and physical properties (eg. size) of a drug can be manipulated to affect its distribution in the body and even contribute to its actual effect (such as the physical size and properties of SPL7013 being responsible for its antiviral effect).

Starpharma has an agreement to collaboratively develop new anti-infective candidates with its partner, Chase-Sun.


DEP ADC'S:

An ADC is an 'antibody-drug conjugate'. An antibody is chemically linked to a drug. The antibody (or antibody fragment, called a nanobody) binds to a target (eg PSMA - prostate specific membrane antigen to treat prostate cancer, or HER2 for some breast cancers and gastric cancer) delivering the drug (or radio-pharmaceutical or radio-diagnostic agent) to where its action is desired, improving efficacy and reducing toxicity of the agent.

Starpharma recently announced an agreement to develop ADCs with Merck, one of the biggest pharmaceutical companies in the worldand has other, as-yet undisclosed, partners in this area. On 16 March 2021, Starpharma announced incredibly exciting preclinical results for one of its ADCs under development: DEP HER2 Lutetium.

ADVANTAGES OF DEP ADC'S:

HIGHER ‘PAYLOAD’ (much higher drug:antibody ratio):

DEP ADCs offer a far superior payload, with multiple linkages per dendrimer molecule/ nanoparticle that can be 'armed' with a drug or radio pharmaceutical (or radio diagnostic) agent compared to current ADC technology. The antibody then only needs the one link on its surface to link it to the dendrimer. This allows the DEP ADC to have a higher drug: antibody ratio than existing ADCs.

From my reading, current ADCs have a limited number of linkages on the actual antibody protein, to which the active agent is bound.

LESS COMPLEX DEVELOPMENT AND MANUFACTURE:

From my reading, current ADCs are very complex to develop and manufacture, due the difficulty of making those linkages of the active agent to the antibody protein complex structure. Each new antibody has a different structure and presents a new complex problem to solve. Starpharma's DEP dendrimers have been linked to many active agents now and it is my understanding that the process is now well understood and it is relatively straightforward to ' reproduce' the process to link new agents. In other words, DEP is a PLATFORM technology: a reproducible process for linking dendrimers to different agents and able to be manufactured cost effectively and at scale.

IMPROVED AND MORE PRECISE DRUG DELIVERY:

As discussed earlier regarding the general advantages of all DEP drugs, DEP ADCs should also offer superior solubility and ' designer' size of the nanoparticle, resulting in superior delivery to where they are most needed (more efficient and targeted delivery), even before the added targeting effect of the antibody, resulting in BETTER EFFICACY and LESS TOXICITY.

ADVANTAGES OF DEP RADIOPHARMACEUTICALS and DEP RADIO-DIAGNOSTIC AGENTS:
Are the same as discussed above for ADCs in general.

Starpharma has the DEP ADCs radio-pharmaceutical DEP Lutetium and DEP HER2 Lutetium, and the DEP ADC radio-diagnostic DEP Zirconium, currently in pre-clinical development (along with other as-yet undisclosed ADCs).

OTHER TYPES OF DRUGS:

Other drugs, such as hormones, can also benefit from DEP technology. For example, Starpharma has existing patents covering DEP insulin.