Actualizo la cartera, bastante movimiento esta semana. Como he ido cantando me he quitado varias que tenía menos convencimiento o que los resultados no tenían buena pinta.
Fuera las GRF con la subida de ayer, prácticamente en even. Aumento los € disponibles y la tesis con las que la compré no parece que tenga mucha fuerza.
De lo que expiró ayer a nombrar en este hilo fueron los 2 putts 3 de AMRN, no querían pagar, ala. SRNE que tenía 3 putts 7 que han rendido rico. Mantengo posiciones en los dos valores. CODX, NVAX y ZYNE no terminan de entrar. Están cerca pero no se cierran. Paciencia.
Si te sientas en la mesa y no descubres al "primo" es que lo eres tú.
Everything that is not core can be dumped for profits if the $XBI gets back to the old high. They are cool companies, but they are not core to my strategy. They are there for trading. They can become core position, but they need to show me the data.
1. CRBU – This company is working to solve all the problems with the first generation of CRISPR gene editors like the potential of mutations from double stranded breaks and off targets from the inaccuracy of the guides. They use a technology that uses a blend of RNA and DNA to build their guides improving on their ability to bind to the DNA while reducing their chances of off target binding. I have been following them for years, and I think they have a very strong management team.
2. CABA – This company is working on CAAR-T cells for auto immune disorders. They create a CAR receptor for the self antigen that B cells become auto reactive to. They put this into a T cell so they can use them to target and kill these self reactive B cells. They have very clean early safety data, but we still need to see the efficacy data. This is like trying to find a needle in a stack of needles with these reactive B cells. The big deal will be can they reach efficacy before they reach a cell dose that gets too high to be commercially profitable. I think 2.5 billion cells would be the limit. If they have to go beyond that, I would walk away. I do like the management team as the CEO is always very cautious on his statements. If this works, it has huge potential in auto immune disorders.
3. KYMR – This company is working on protein degraders around inflammation and oncology. Their lead candidate is for IRAK4 which could have big indications for both inflammation and oncology. The early bio marker data looks very promising. They have other protein degraders in the pipeline like STAT3. The potential for protein degraders to be very safe and very easy to administer makes them very promising. I only just started to follow this management team so I don't know them very well.
4. RVMD – This company has one of the hottest science programs I have ever seen around pathways. They are highly focused on the key growth pathways with MAPK and mTOR. These pathways have been untouched for many years as it is very hard to target cancer mutations in these pathways vs healthy tissue. The revolution in genetics has lead to the first in roads into these pathways with the KRAS inhibitors and the PI3K inhibitors. There is so much to be developed in these pathways. The one thing that has emerged is the higher upstream in the pathway the target is the more toxicity. They are working on drugs across all stops in these pathways. They will be developing and combining these new pathway drugs to find great combinations. It is very early and all these new targets could fail. If they succeed, then these are some of the biggest targets in any pathways ever. Mutations in the MAPK pathway are represented in 40% of all cancers.
5. GBIO – This company is working of guided LNP technology that will allow LNP to go to tissues beyond the liver. They are also developing it to allow for redosing of gene therapies. They have some promising early preclinical data around ability to dose up the level of protein expression to any desired level. Then they can treat with a booster dose only when needed over time. This is the first real treatment for gene therapies that addresses the long term cure. They have a long way to go to prove this science, but they could completely change the gene therapy landscape.
6. IPSC – This company is working on off the shelf cell therapies using induced pluipotent stem cells technology. They have four early stage drug candidates around CAR-NK and CAR-T therapies. They have developed edits to these cells to mask them from the immune system like knocking out MHC, replacing MHC with HLA-E and up regulating CD47. They have a ton of potential with their technology they licensed from the already commercial Fuji Film cell therapy manufacturing.
7. FDMT – This company takes the AAV vector and hyper mutates it to find new strains of the virus. They are working to develop new viral vectors that have better distribution to tissues and stronger efficacy. They are also working to find strains that have no immunity. The early models show strong distribution of these new vectors into the eye and heart. They have programs for XLRP, wet AMD and Fabry. There is a huge need for newer and better AAV vectors for gene therapy. There is a huge amount of potential for them just in wet AMD. It could get even bigger if they work in all the tissues they are working on.
8. RPTX – This company is working on Synthetic Lethality around DNA Damage Repair (DDR) pathways. This exploits the natural genetic instability of the cancer cells and uses it against them. They find key DDR pathways with mutations in cancers like ATM/ATR or CCNE, and they find another pathway they can inhibit that will push that cell into so unstable that it dies. This is some very promising new science. They have two programs working their way into the clinic. There is a lot of potential behind these types of mutations. Its a whole new approach to cancer genetics. I think this will become on of the hottest spaces in the next few years. That makes this a potential take out target for a big cap company who wants into this Synthetic Lethality space.
9. TIL – This is a new early stage Tumor Infiltrating Lymphocyte company. These therapies have been extremely powerful in solid tumors. They extract a tumor and use it to create a polyclonal T cell treatment targeting just the mutations for that tumor. They then infuse the TIL back into the patient to treat all the metastasis. They have solid data with high response rates and over 2 years of durability on treatment. This company is an early stage TIL company with very powerful early data in a phase 1 compassionate use trial that put up 67% response rates. They also have a CoStar program that is designed to edit future cell lines of TIL to give them additional benefits.
10. SANA – This company has two technology platforms which gives them even more potential, but also more risk. Their first platform is around fusosome delivery. They are designing Virus Like Particles (VLP) which are guided by ligands to desired tissues. They use fusion proteins to make cell entry instead of receptor mediated endocytosis. This has the potential to edit inside a person. They are testing this with creating CAR-T cells inside the patients without all the lengthy harvesting, editing and lymphodepletion. Its still very much in the concept phase so anything can go wrong. They also have a hypoimmune iPSC platform that is designing cells that are able to work without any immune response or lymphodepletion needed. They are using things like knocking out MHC and replacing it with HLA-E. They are also using up-regulation of CD47 to block macrophages. I think they have the biggest potential of any company I have ever discovered. They also have the highest risk as all this technology is new and not validated.
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My list of Protein Degraders is_
KYMR for its huge IRAK4 potential
GLUE for its huge NLRP3 potential
CCCC for its great pathway targets like IKFZ1/3 and EFGR
ARVN because it might get around to Tau or KRAS someday lol
PROTAC is bi valent protein degraders. Many of these companies are mono valent or do both. Calling a protein degrader companies PROTAC is a bit off. Just for the FY
