There seem to be a gathering group of new people to the world of Phylogica here and in the market. I obtained a private analyst style note about a month or 2 ago that helped me understand further the basic potential from a blended view of science an commerciality and judging by the comments of new and old holders it might provide some helpful perspective - please note that it is not from the company so it may not reflect the direction they are taking at all but it might help us understand just what the potential is and why they seem to be taking the direction they are.
What I have done is heavily plagiarised it into edited form to share here. I hope it helps but I'd just take it as 'PYC for dummies' if I were you as you could have got all this info my reading the right threads here and reading the company documents and added a little opinion.
Disclosure - I hold heaps and have been buying for the past 2 years - I really don't care if you buy or sell but I owe my success to good decisions based primarily on information people shared on forums over the past 18 years so I continue to share.
Phylogica’s iMyc program overview & other potential
Phylogica is a platform technology company whose core asset is a library made up of protein fragments expressed from the genetic material of micro-organisms (Phylomers). The idea behind using this as a source of drug candidates is that the sequences and structures found in nature are highly evolved and are therefore likely to be enriched for proteins that have the ability to interact with the human body in a manner that yields therapeutic benefit.
The company has spent the last decade developing screening technologies to select the few peptides from within the libraries that are able to:
i) cross the cell wall and gain access to the intracellular space (where there are many more targets for drugs than on the outside of cells); and
ii) interact with the high value targets that exist on the inside of cells.
The peptides that have the ability to cross the cell wall are known as Functional Penetrating Peptides (FPPs) and these FPPs are able to ‘carry’ a large molecule (such as an active intracellular drug cargo) into an environment to which it could not otherwise gain accessbecause of its large size. The ability to provide access for large molecules to intracellular drug targets is a major step forward because of the greater sensitivity and specificity that interacting with these targets affords (resulting in better drugs with fewer side effects). To exploit this development, Phylogica have identified drug cargoes from within their libraries active against the highest value intracellular target (Myc – discussed below) and are fusing these to an FPP to create a Myc inhibitor (iMyc) for the treatment of cancer.
(Abbreviations)
FPP (Functional Penetrating Peptide) – a peptide with the ability to cross the cell wall and access the intracellular environment. These FPPs ideally have no pharmacological activity of their own once inside the cell but rather can ‘carry’ a drug cargo with this property into the cell with them.
Myc - the ‘super-controller’ found on the inside of cells responsible for ‘driving’ most human cancers.
iMyc (Myc inhibitor) –Phylogica’s proprietary drug cargoes that directly inhibit Myc when carried inside cells by Phylogica’s proprietary FPPs.
Myc as a drug target
Cancer Research UK (CRUK) has identified the inhibition of Myc as one of its ‘Grand Challenges’ because of its promise as a breakthrough in cancer treatment. CRUK describe the challenge of Myc inhibition in the following terms:
‘Researchers already know how to theoretically cure a significant proportion of all human cancers. The problem is actually doing it.
At the heart of this challenge lies a molecule called MYC. In the same way that a conductor directs all the various parts of an orchestra to work together in harmony, MYC co-ordinates the actions of many different genes inside cells to keep things running smoothly.’
https://www.cancerresearchuk.org/fu...earch/grand-challenge-award/challenge6?wssl=1
http://scienceblog.cancerresearchuk...hallenge-six-target-cancers-super-controller/
Myc holds the key to a ‘cure’ for cancer
Researchers have recently been able to demonstrate the effect that an iMyc would have if it could be delivered into tumour cells (using a genetic model of disease). These experiments demonstrate (in CRUK’s own words) that: ‘When these animals developed lung cancer, turning off MYC completely killed the cancer cells’. This was not the only remarkable observation to emerge from the experiments – CRUK also commented on the side effect profile of the modelled treatment: ‘Importantly, the treatment only caused mild, reversible side effects’.
http://genesdev.cshlp.org/content/27/5/504.abstract
The attractiveness of Myc as a drug target is well understood and: ‘These remarkable results [have] re-ignited interest in targeting MYC as a potential cancer cure’.
http://www.thelancet.com/education/at-the-limits/oncology-2015/myc-in-cancer
Note: Each animal in the above experiments had between 50 and 100 primary tumours at all stages of disease progression making the fact that they were ‘disease-free’ following episodic Myc inhibition even more impressive (See minutes 15 through 20 of the Gerard Evans presentation from the video link above)
What is required to successfully drug Myc?
There are two basic requirements for an effective direct inhibitor of Myc:
i) access to the environment where Myc is present (the nucleus of the cell); and
ii) the ability to bind to Myc in a manner that effectively limits its ability to function.
One major reason that Myc has previously been considered ‘undruggable’ is ‘that the protein expressed by the Myc gene does not lend itself to conventional drug discovery approaches – it has no deep ‘pockets’ like many other cancer drug targets and carries out its role through fleeting interactions with other proteins’. Small molecules that have the ability to cross the cell membrane can’t adequately bind to Myc and the large molecular weight biologic drugs that could bind to Myc don’t have the ability to cross the cell membrane. Phylogica addresses these barriers in a ‘modular’ format by using its FPP to overcome the delivery problem and leaving the iMyc to bind to and inhibit Myc.
Phylogica’s competitive position
Phylogica’s FPPs are approximately 50 times more potent than the previous gold standard in intracellular delivery (a molecule derived from HIV known as TAT). Phylogica’s iMycs are equivalent to or better than the current gold standard Myc inhibitor known as OmoMyc and this is before they have been through the ‘lead optimisation’ process which aims to increase their potency by 100 to 1,000 fold.
If successful in its lead optimisation efforts (first half CY2017) Phylogica will, therefore, have the world’s most potent iMyc (that is several orders of magnitude more effective than the current gold standard). Phylogica has already seen marked reductions in tumour volumes in animal models of disease after treatment with a systemically delivered unoptimised drug conjugate.
Commercial relevance
The window for commercialisation of Phylogica’s iMyc program opens with the entry into a formal pre-clinical program in late 2017. The delivery of the ‘data pack’ from the lead optimisation phase that will be used to enter a formal pre-clinical development program is widely acknowledged as being the critical trigger for PharmaCo interest in the program. These comparable deals done at the pre-clinical phase in 2016 demonstrate that Phylogica might expect somewhere between $50-100m USD up-front with approximately $1bn USD of trailing milestones for a successful pre-clinical iMycprogram.
http://www.fiercebiotech.com/biotech/jounce-nabs-first-big-deal-2-6b-i-o-tie-up-celgene
http://www.fiercebiotech.com/biotech/abbvie-argenx-sign-685m-preclinical-immuno-oncology-deal
http://www.fiercebiotech.com/biotec...l-i-o-tie-up-small-cap-advaxis-for-up-to-540m
The critical objective for Phylogica throughout the pre-clinical development phase, however, will be to demonstrate the broad application of its iMyc program as a complement to the immuno-oncology drugs currently in development (these drugs ‘hit the brakes’ on tumour progression). Myc inhibition acts via an alternative mechanism akin to ‘taking the foot off the accelerator’. These two distinct mechanisms of action are complementary and therefore Phylogica’s iMyc could be used in combination with a broad range of immuno-oncology candidates. The deal terms available for drug candidates with this breadth of application are far more favourable as demonstrated by the $800m USD up-front (plus $425m USD trailing) paid to Flexus for their pre-clinical candidate.
http://www.fiercebiotech.com/financ...mmunotherapy-1-25b-buyout-of-fledgling-flexus
Flexus CEO Terry Rosen justified the higher than usual terms for this acquisition by pointing to the ability of Flexus’ leadcandidate to be combined with multiple other drugs: "We had a data set that suggested it has the potential to be best-in-class, with the ability for a partner to combine it with many other assets. If you look at any company working in oncology, it can potentially increase the value of a whole portfolio of assets. It could be multiplicative and that creates a big valuation".
Those comments are equally applicable not only to Phylogica’siMyc program but also more generally to the ability of the Phylomers to provide access to intracellular targets (ie. Use of the FPPs as a delivery modality).
Other applications of the Phylomer libraries
There are at least three further applications of the Phylomer library that have the potential to add substantial value to Phylogica beyond the iMyc program. Broadly, these include:
1) pursuit of other high value intracellular targets through internally controlled programs;
2) licensing of the delivery peptides (FPPs) to third parties for delivery of their own drug cargoes in non-competitive fields (eg. Genetic diseases outside of oncology such as the collaboration with Murdoch University aimed at treating Duchenne’s Muscular Dystrophy or oncology programs directed towards non-competitive intracellular targets); and
3) utilisation of the Phylomer libraries against non-human cell lines such as the company’s existing USD140m collaboration with Genentech directed towards the treatment of drug-resistant micro-organisms.
Phylogica has two other active drug development programs against high value targets (Stat5 and YB1) andare looking tol initiate further programs against new targets in 2017. The objective here is to have multiple different programs at different stages of development so that if individual assets (like the iMyc program) are sold, the unique properties of the Phylomerlibraries can continue to be exploited for the benefit of Phylogica shareholders (again, similar to the Flexusacquisition described above where all assets other than the individual drug program were retained by the company after the USD1.25bn sale of the lead drug candidate).
(20min delay)