#127385
Re: Farmas USA
b2k
Magnificent 7
1. BPMC - This company is the top dog in targeting tryrosine receptor kinases. These are drugs that target the kinase on the inside of the cell receptor. This can basically shut off the receptor right at the root. There are many cell receptors for cell growth signals that mutate to drive cancer. Some of them are PDGFRa, KIT, RET and EFGR. 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. There Systemic Mastocytosis is 95% driven by KIT D816V mutations. They have a very high response rate of over 80% for these patients. They also have a RET drug in Pralsetinib which has great data in NSCLC and MTC. 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 group of EFGR drugs in early development that target double resistant and triple resistant EFGR mutations. The preclincal data was very exciting.
2. TPTX - They have a platform of small molecule kinase inhibitors. These are much smaller then other kinase inhibitors. This leads to far less toxicity and the ability to avoid resistance. Many kinases will develop mutations over time when exposed to kinase inhibitors to develop resistance to those inhibitors. There are two common mutations with the gatekeeper mutation and the solvent front mutation. The kinase inhibitors developed by Turning Point are small enough to bind into the ATP pocket without contacting these mutations. This has lead to some very impressive data so far with lower side effects. This is another technology platform that could change the way we do kinase inhibitors. I call it the second generation of kinase inhibitors. The data so far has been very impressive. They have 90% ORR in ROS1 mutated NSCLC. They had some early data in MET that was promising. They have RET data coming up soon. They have an early ALK program. I think Repotrectinib could do up to $500 million in NSCLC with room to grow in other indications.
3. GBIO - This is my new top pick as they are solving the really important problem with delivery for gene therapies. They are a new generation of gene therapy. One that offers real long term cures. I know its really early, but I just loved their preclinical data. They can target 10% factor expression of any protein. Then they just dose every few weeks until the patient reaches the desired level of expression. As the gene therapy fades, they can do booster dose to bring the levels back up. This offers real life long gene therapies where gene editing may never work in-vivo without mutations. I think their pipeline has unlimited potential to go back and do every gene therapy the right way. This is clearly a platform company that can yield many new drugs.
4. BCAB - This company conditionally activated antibodies. These antibodies are designed to become activated in the low pH environment of the tumor but not anywhere else. The early phase 1 data showed an amazing safety profile using these antibodies with Antibody Drug Conjugates (ADC). This is the most impressive safety profile I have ever seen for an ADC. They didn't just do it with one they did it with two ADC programs around AXL and ROR2. There was still on target toxicity, but no off target toxicity was found. I think they have a platform that can yield many new drugs. They could change the whole way we do antibodies and ADCs.
5. CABA – This is my new number three pick. They are a very speculative company, but they have a technology that could be a big deal. They create CAR-T cells that express antigen for auto reactive B cells. This allows them to target and deplete these reactive B cells that drive auto immunity. It is one of those technologies that will either work or it won't. The key will be if these CAAR-T cells will be able to deplete the memory B cells for and effective cure. That is why I am urging caution on this one, but I think it is really works as a small bet at such a cheap valuation. If the technology works, its a platform that can yield many new drugs.
6. FDMT – This is a new gene therapy company working on discovery of new viral vectors based on the AAV type. They use a system to rapidly mutate and screen variants to look for new vectors which have low immune profiles or which can reach new tissues. They have an early program around the eye and heart with new vectors that have extremely high transfection and tissue coverage. The hope is this will lead to far higher protein production and better therapies. They started with tissues that don't turn over like eye and heart muscle so these gene therapies should persist for the entire life of the patient. I think this is a fascinating program, but its still very early, and we need to see more data.
7. TCRR – This is a new company focused on autologous and allogeneic CAR-T therapies. They have unique technology which attaches the CAR receptors to the CD-3 of the natural T cell complex. This technology allows the CAR receptors to activate the T cell complex in a natural manor. This provides many additional benefits over other CAR-T insertion technologies. It promotes a more natural cell activation, behavior and persistence. The current form of the technology is being used as autologous as the original T cell receptor is left intact. The next generation of these cells will edit the T cell receptor to creating an allogeneic product. They can even use them in a bi-specific manor having the TCR target one antigen and the CAR targeting another. This would dramatically reduce off target effects. This is very early technology, but the first data in Mesothelioma showed a single agent ORR of 40%. That is very impressive data so far. This is another platform that can be used to make many drugs for many different indications.
2. TPTX - They have a platform of small molecule kinase inhibitors. These are much smaller then other kinase inhibitors. This leads to far less toxicity and the ability to avoid resistance. Many kinases will develop mutations over time when exposed to kinase inhibitors to develop resistance to those inhibitors. There are two common mutations with the gatekeeper mutation and the solvent front mutation. The kinase inhibitors developed by Turning Point are small enough to bind into the ATP pocket without contacting these mutations. This has lead to some very impressive data so far with lower side effects. This is another technology platform that could change the way we do kinase inhibitors. I call it the second generation of kinase inhibitors. The data so far has been very impressive. They have 90% ORR in ROS1 mutated NSCLC. They had some early data in MET that was promising. They have RET data coming up soon. They have an early ALK program. I think Repotrectinib could do up to $500 million in NSCLC with room to grow in other indications.
3. GBIO - This is my new top pick as they are solving the really important problem with delivery for gene therapies. They are a new generation of gene therapy. One that offers real long term cures. I know its really early, but I just loved their preclinical data. They can target 10% factor expression of any protein. Then they just dose every few weeks until the patient reaches the desired level of expression. As the gene therapy fades, they can do booster dose to bring the levels back up. This offers real life long gene therapies where gene editing may never work in-vivo without mutations. I think their pipeline has unlimited potential to go back and do every gene therapy the right way. This is clearly a platform company that can yield many new drugs.
4. BCAB - This company conditionally activated antibodies. These antibodies are designed to become activated in the low pH environment of the tumor but not anywhere else. The early phase 1 data showed an amazing safety profile using these antibodies with Antibody Drug Conjugates (ADC). This is the most impressive safety profile I have ever seen for an ADC. They didn't just do it with one they did it with two ADC programs around AXL and ROR2. There was still on target toxicity, but no off target toxicity was found. I think they have a platform that can yield many new drugs. They could change the whole way we do antibodies and ADCs.
5. CABA – This is my new number three pick. They are a very speculative company, but they have a technology that could be a big deal. They create CAR-T cells that express antigen for auto reactive B cells. This allows them to target and deplete these reactive B cells that drive auto immunity. It is one of those technologies that will either work or it won't. The key will be if these CAAR-T cells will be able to deplete the memory B cells for and effective cure. That is why I am urging caution on this one, but I think it is really works as a small bet at such a cheap valuation. If the technology works, its a platform that can yield many new drugs.
6. FDMT – This is a new gene therapy company working on discovery of new viral vectors based on the AAV type. They use a system to rapidly mutate and screen variants to look for new vectors which have low immune profiles or which can reach new tissues. They have an early program around the eye and heart with new vectors that have extremely high transfection and tissue coverage. The hope is this will lead to far higher protein production and better therapies. They started with tissues that don't turn over like eye and heart muscle so these gene therapies should persist for the entire life of the patient. I think this is a fascinating program, but its still very early, and we need to see more data.
7. TCRR – This is a new company focused on autologous and allogeneic CAR-T therapies. They have unique technology which attaches the CAR receptors to the CD-3 of the natural T cell complex. This technology allows the CAR receptors to activate the T cell complex in a natural manor. This provides many additional benefits over other CAR-T insertion technologies. It promotes a more natural cell activation, behavior and persistence. The current form of the technology is being used as autologous as the original T cell receptor is left intact. The next generation of these cells will edit the T cell receptor to creating an allogeneic product. They can even use them in a bi-specific manor having the TCR target one antigen and the CAR targeting another. This would dramatically reduce off target effects. This is very early technology, but the first data in Mesothelioma showed a single agent ORR of 40%. That is very impressive data so far. This is another platform that can be used to make many drugs for many different indications.
