Andrew Pannu’s Post

Cell therapy is in the middle of a huge shift... ...and everyone from small biotechs to big pharma want in on the next big thing: autoimmune disorders Here's how I think this goes down: First, I charted the programs of 37 companies in this space, segmented by cell source and modality Exhibit 1: Cell Therapy I&I Landscape This is one of the fastest growing spaces in the industry - dozens of formerly oncology-focused cell therapy companies have pivoted their portfolios entirely, and you have to imagine that dozens more are having serious conversations At minimum, it seems everyone needs to have some presence given investor enthusiasm. And it makes sense why: • There are 100+ known autoimmune diseases with rising incidence due to lifestyle, environmental factors and improved diagnosis - this equals 15-20M Americans and 4.5% of the world's population • Most indications have suboptimal treatments and those that do have a large base of refractory patients for whom existing MoAs don't work • Unlike most cancers, I&I patients can be young, meaning a near-curative therapy option has a lifetime of benefit and cost savings • It's a massive market with $100B in aggregate economic burden; for context, the US has 80K annual NHL cases vs. >1M SLE cases And the oncology cell therapy space is tough right now - an explosion of funding has created way too many companies pursuing similar innovations. Cheaper novel alternatives such as BsAbs + persistent supply & manufacturing issues have dampened enthusiasm of ever reaching frontline patients Autoimmunity is comparably a blue ocean - not only with no approved therapies, but essentially no assets in late-stage development. A lot of the learnings around B-cell mediated diseases can be ported over, and first movers could get a nice M&A premium that the space has been missing For all of those reasons, I think we'll see more new companies spin up platforms around this + retooling of existing platforms. Big Pharma will not take a wait-and-see approach either: I expect them to continue to prioritize their internal programs (we already see a few) and lean into their manufacturing and supply chain edge + commercial learnings The rules of the game are a bit different than in oncology: safety is paramount given this is not life-or-death. Similarly, vein-to-vein time is not as important - it's not a race against a growing tumor to get the drug to patients Initially, we'll see companies start with validated targets and indications - of the 70+ programs, >70% involve CD19 or BCMA and most target SLE, since PoC data has already emerged there. Autologous CAR-Ts are a popular choice. As the space becomes more crowded, we'll quickly see more innovation, including: • Larger indications without PoC (i.e. RA, IBD, MS) • Alternate modalities, such as Tregs or NK cells • Allogeneic and in vivo approaches, which offer significant manufacturing advantages Let me know how you think this space evolves or if you'd like a PDF!

Cell therapy is in the middle of a huge shift... ...and everyone from small biotechs to big pharma want in on the next big thing: autoimmune disorders Here's how I think this goes down: First, I charted the programs of 37 companies in this space, segmented by cell source and modality Exhibit 1: Cell Therapy I&I Landscape This is one of the fastest growing spaces in the industry - dozens of formerly oncology-focused cell therapy companies have pivoted their portfolios entirely, and you have to imagine that dozens more are having serious conversations At minimum, it seems everyone needs to have some presence given investor enthusiasm. And it makes sense why: • There are 100+ known autoimmune diseases with rising incidence due to lifestyle, environmental factors and improved diagnosis - this equals 15-20M Americans and 4.5% of the world's population • Most indications have suboptimal treatments and those that do have a large base of refractory patients for whom existing MoAs don't work • Unlike most cancers, I&I patients can be young, meaning a near-curative therapy option has a lifetime of benefit and cost savings • It's a massive market with $100B in aggregate economic burden; for context, the US has 80K annual NHL cases vs. >1M SLE cases And the oncology cell therapy space is tough right now - an explosion of funding has created way too many companies pursuing similar innovations. Cheaper novel alternatives such as BsAbs + persistent supply & manufacturing issues have dampened enthusiasm of ever reaching frontline patients Autoimmunity is comparably a blue ocean - not only with no approved therapies, but essentially no assets in late-stage development. A lot of the learnings around B-cell mediated diseases can be ported over, and first movers could get a nice M&A premium that the space has been missing For all of those reasons, I think we'll see more new companies spin up platforms around this + retooling of existing platforms. Big Pharma will not take a wait-and-see approach either: I expect them to continue to prioritize their internal programs (we already see a few) and lean into their manufacturing and supply chain edge + commercial learnings The rules of the game are a bit different than in oncology: safety is paramount given this is not life-or-death. Similarly, vein-to-vein time is not as important - it's not a race against a growing tumor to get the drug to patients Initially, we'll see companies start with validated targets and indications - of the 70+ programs, >70% involve CD19 or BCMA and most target SLE, since PoC data has already emerged there. Autologous CAR-Ts are a popular choice. As the space becomes more crowded, we'll quickly see more innovation, including: • Larger indications without PoC (i.e. RA, IBD, MS) • Alternate modalities, such as Tregs or NK cells • Allogeneic and in vivo approaches, which offer significant manufacturing advantages Let me know how you think this space evolves or if you'd like a PDF!

Cell therapy is in the middle of a huge shift... ...and everyone from small biotechs to big pharma want in on the next big thing: autoimmune disorders Here's how I think this goes down: First, I charted the programs of 37 companies in this space, segmented by cell source and modality Exhibit 1: Cell Therapy I&I Landscape This is one of the fastest growing spaces in the industry - dozens of formerly oncology-focused cell therapy companies have pivoted their portfolios entirely, and you have to imagine that dozens more are having serious conversations At minimum, it seems everyone needs to have some presence given investor enthusiasm. And it makes sense why: • There are 100+ known autoimmune diseases with rising incidence due to lifestyle, environmental factors and improved diagnosis - this equals 15-20M Americans and 4.5% of the world's population • Most indications have suboptimal treatments and those that do have a large base of refractory patients for whom existing MoAs don't work • Unlike most cancers, I&I patients can be young, meaning a near-curative therapy option has a lifetime of benefit and cost savings • It's a massive market with $100B in aggregate economic burden; for context, the US has 80K annual NHL cases vs. >1M SLE cases And the oncology cell therapy space is tough right now - an explosion of funding has created way too many companies pursuing similar innovations. Cheaper novel alternatives such as BsAbs + persistent supply & manufacturing issues have dampened enthusiasm of ever reaching frontline patients Autoimmunity is comparably a blue ocean - not only with no approved therapies, but essentially no assets in late-stage development. A lot of the learnings around B-cell mediated diseases can be ported over, and first movers could get a nice M&A premium that the space has been missing For all of those reasons, I think we'll see more new companies spin up platforms around this + retooling of existing platforms. Big Pharma will not take a wait-and-see approach either: I expect them to continue to prioritize their internal programs (we already see a few) and lean into their manufacturing and supply chain edge + commercial learnings The rules of the game are a bit different than in oncology: safety is paramount given this is not life-or-death. Similarly, vein-to-vein time is not as important - it's not a race against a growing tumor to get the drug to patients Initially, we'll see companies start with validated targets and indications - of the 70+ programs, >70% involve CD19 or BCMA and most target SLE, since PoC data has already emerged there. Autologous CAR-Ts are a popular choice. As the space becomes more crowded, we'll quickly see more innovation, including: • Larger indications without PoC (i.e. RA, IBD, MS) • Alternate modalities, such as Tregs or NK cells • Allogeneic and in vivo approaches, which offer significant manufacturing advantages Let me know how you think this space evolves or if you'd like a PDF!

Cell therapy is in the middle of a huge shift... ...and everyone from small biotechs to big pharma want in on the next big thing: autoimmune disorders Here's how I think this goes down: First, I charted the programs of 37 companies in this space, segmented by cell source and modality Exhibit 1: Cell Therapy I&I Landscape This is one of the fastest growing spaces in the industry - dozens of formerly oncology-focused cell therapy companies have pivoted their portfolios entirely, and you have to imagine that dozens more are having serious conversations At minimum, it seems everyone needs to have some presence given investor enthusiasm. And it makes sense why: • There are 100+ known autoimmune diseases with rising incidence due to lifestyle, environmental factors and improved diagnosis - this equals 15-20M Americans and 4.5% of the world's population • Most indications have suboptimal treatments and those that do have a large base of refractory patients for whom existing MoAs don't work • Unlike most cancers, I&I patients can be young, meaning a near-curative therapy option has a lifetime of benefit and cost savings • It's a massive market with $100B in aggregate economic burden; for context, the US has 80K annual NHL cases vs. >1M SLE cases And the oncology cell therapy space is tough right now - an explosion of funding has created way too many companies pursuing similar innovations. Cheaper novel alternatives such as BsAbs + persistent supply & manufacturing issues have dampened enthusiasm of ever reaching frontline patients Autoimmunity is comparably a blue ocean - not only with no approved therapies, but essentially no assets in late-stage development. A lot of the learnings around B-cell mediated diseases can be ported over, and first movers could get a nice M&A premium that the space has been missing For all of those reasons, I think we'll see more new companies spin up platforms around this + retooling of existing platforms. Big Pharma will not take a wait-and-see approach either: I expect them to continue to prioritize their internal programs (we already see a few) and lean into their manufacturing and supply chain edge + commercial learnings The rules of the game are a bit different than in oncology: safety is paramount given this is not life-or-death. Similarly, vein-to-vein time is not as important - it's not a race against a growing tumor to get the drug to patients Initially, we'll see companies start with validated targets and indications - of the 70+ programs, >70% involve CD19 or BCMA and most target SLE, since PoC data has already emerged there. Autologous CAR-Ts are a popular choice. As the space becomes more crowded, we'll quickly see more innovation, including: • Larger indications without PoC (i.e. RA, IBD, MS) • Alternate modalities, such as Tregs or NK cells • Allogeneic and in vivo approaches, which offer significant manufacturing advantages Let me know how you think this space evolves or if you'd like a PDF!