b2k Top 10 ideas:
My top 10 updated
Since I sold KRYS, I felt it was important to replace it on my top 10. That doesn't mean I don't still follow and like KRYS. I just wanted to move on to something else. Here in my new top 10. Spoiler Alert: I replaced it with MNTA which has far more potential long term and has a bit more development behind them. It also gives me a good spread across all my different science categories with 2 antibody companies.
My Top 10 Ideas
1. FATE - This is my top pick for its cell therapies with their induce pluripotent stem cell program. This technology offers the potential to change the way we mass produce cell therapies for T and NK cells. They take stem cells and develop them with cytokines along with CRISPR gene editing down the lineage to the cells they want. Only a few cells get all the edits they desire, but they pick them out and build master banks of these cells. Then all they need to do is continue to stimulate them to divide producing more and more of the desired cells with all the edits they want. They have several programs around NK cells with each generation containing more edits. The first is FT-500 which is a completely natural NK cell. Then comes FT-516 which has the enhanced CD-16 antibody receptor. The next is FT-538 which adds the IL-15 and CD38 knockout. The FT-596 NK cells include the CAR receptor for anti CD-19. They do have their first CAR-T cell in development with FT-819. They are doing a CD-19 inserted into the TRAC locus. The next generation should include additional edits like PD-1 knockout. The data here is still very early, but it has shown very good promise.
2. CRSP - This is one of my top picks for its gene editing and my only pick in CRISPR technology. This is my top pick because I think Sam Kulkarni has great vision to where he wants CRSP to go. I think CRISPR technology has the potential to change the way we do cell engineering. It is fast, easy and very cheap. It still has a bunch of obstacles in being used in a human being, but it has so much potential in the ex-vivo cell editing space. It could be worth a few billion in potential in T cell and stem cell editing. The combining of induced pluripotent stem cells with the ability to guide cell development with CRISPR editing could revolutionize regenerative medicine. We could someday grow entire organs from a few stem cells. Right now, CRISPR has huge hopes and dreams with very little data. The first patients in Beta Thalassemia and Sickle Cell did look very strong.
3. MRNA – This is my newest pick. They are developing RNA based technologies. They have two different approaches to immunity. The first inserts a messenger RNA (mRNA) that encodes and antibody. This provides passive immunity for a period of time. The second approach inserts a mRNA that uses the cells to encode viral proteins. These proteins can then be presented by the cell to the immune system to provoke a response. This can build memory cells and lasting immunity. The data from both types of programs has been impressive so far. They can use these technologies to target any viral proteins for any virus. The basic technology works so all they have to do is find the best antigens for a virus to target that will provoke the best response. Their lead drug is for CMV which is one of the leading causes of birth defect world wide. They have a very strong program here and it could do over $1 billion a year in sales.
4. BPMC - This company is the top dog in targeted therapies. They have multiple breakthrough therapy programs. Its lead drug Avapritinib is a PDGFRa/KIT drug. It is highly designed to target D842V and D816V mutations of GIST and KIT. They have strong data in the exon 18 mutation for GIST and Systemic Mastocytosis. The Exon 18 GIST is not a very large indication and just got approval. Then they have Avapritinib in Systemic Mastocytosis. This is a terrible genetic disorder where mast cells go wild. They have a very high response rate of over 80% for these patients. This indication could be worth about $750 million. They also have a RET drug in Pralsetinib which has great data in NSCLC and MTC. This could be worth about $500 million. Plalsetinib is submitted for second line NSCLC and should be submitted for second line MTC this year. They could have 4 commercial drugs by the end of 2021 and well on their way to $1 billion in revenues in a few years. They have a FGFR4 inhibitor in early clinic with Fisogatinib. There is limited data in this program so far. They just began a new set of programs around EFGR mutations.
5. IOVA - They work on cell therapies around Tumor Infiltrating Lymphocytes (TIL). The data they had at ASCO last year was just amazing. They extract cells from tumor in metastatic Melanoma, Cervical Cancer and Head & Neck Cancers. They isolate the tumor antigens and introduce them to the patients immune cells in culture along with IL-2 to activate the T cells. This bypasses the high toxicity of IL-2 and creates natural T cells vs the tumor antigens. They infuse the cells back into the patient which go to work clearing all the mets. This had an impressive 50% response rate. This could be one of the big ways we approach solid tumors going forward. It won't be the only way since many tumors don't have Tumor Infiltrating Lymphocytes to start with. It also requires them to still address the Tumor Microenvironment with checkpoint inhibitors. They recently began development of a Peripheral Blood Mononuclear Cells program.
6. DCPH - They have Ripretinib which is a PDGFRa/KIT inhibitor. This is more of a pan inhibitor of these targets vs a more selective inhibitor in Avapritinib. Ripretinib has good efficacy in 4th line GIST now and it up for approval on August 13th. It has a very high improvement in PFS which is very promising. It also seems to have a clean safety profile. I think Ripretinib could do up to $500 million in the GIST indications. They don't have any data yet in Systemic Mastocytosis which is the biggest indication for Ripretinib. They also have a few early stage drugs in development around Rebastinib for TIE2. They have some encouraging data from this program in combination with Paclitaxel and Carboplatin across Breast, Endometrial, Ovarian, and Mesothelioma. They have DCC-3014 for CSF1R. They have only very early data for this program in Tenosynovial Giant Cell Tumor. They announced another new preclinical program last year for ULK which regulate cell Autophagy. That could be a very interesting program when we start to see some data. They are moving that to the clinic this year.
7. ARGX - They have a very impressive pipeline of antibodies targeting autoimmune disorders. Their main drug is an antibody that targets the FcRn receptor. Efgartigimod will bind to and eliminate antibodies involved in auto immune disorders. This is in development in several indications and could earn billion in revenues. They have a second drug in early development with an antibody targeting C2 of the complement system. They have several other program that are in partnership. They have 4 big cap partnerships with Janssen, Leo, Abbvie and Staten.
8. MRTX - They have a multikinase inhibitor in Sitravatinib. I wasn't a big fan of this drug due to its low overall response rate in the low 22% range. It wasn't until I discovered that this drug can rescue patients who have become resistant to checkpoint inhibitors. That is a very big deal. The drug is in development for multiple indications in combination with checkpoint inhibitors. This includes NSCLC, Head & Neck Cancer, Bladder and Renal Cancers to name a few. It could be worth up to about $800 million if all indications work out. They also have an early stage KRAS inhibitor with MRTX-849. This drug could offer big potential in KRAS G12C mutant cancers around NSCLC and CRC. This could be worth $1 billion or more. So far the early data is showing promise. They also have another early KRAS drug for targeting G12D mutations.
9. MNTA – This company has a pipeline around antibody technologies. They have their lead drug that is in development for FcRn receptor. They just had good data recently in Myasthenia Gravis. They are focused more on the glycosylation of antibodies and how they are handled by the immune system with their Fc regions. They have another drug in development for hypersialyated IgG. This drug is in earlier development. Nipocalimab can be worth several billion depending on how many of its indications pan out. They have a lot of potential, but they still have a way to go in devlopment.
10. BEAM - This is a very early stage company with a unique new approach to CRISPR gene editing. They use the CRISPR system linked to a special enzyme structure. This allows them to edit one base pair at a time without any double stranded breaks. This is a fascinating new way to take on gene editing. They can also use many of these at once to do vast rewriting of the
DNA just one nucleotide at a time using multiplex editing. They are also using the technology to edit the promoter regions to either science or reactive silenced genes. There is only preclinical data so far for Beta Thalassemia and Sickle Cell disease. So far, they are showing 60% Fetal Hb production which is far above any other in this space.
