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Epsiode 234 - Lei Fang CEO Excalipoint · The BioHub - by Avetix

• 0:06
  Welcome back to another episode of the Biohop podcast.
• 0:09
  Today I'm thrilled to be joined by Lee Fang, who is the Co
• 0:12
  founder and CEO of Excalapoint. In today's episode, we're going
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  to talk a little about Lee's career and the work that
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  Excalapoint are doing in the T cell engager space.
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  Lee, thank you so much for coming on and joining us.
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  Hi, George. It's very appreciate to give us
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  the opportunity to talk about our story and our science and
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  what do we do. So I'm Leifang and you can call
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  me late. I was trained in Chinese kind of
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  a science as AT cell immunologist and which is a
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  little bit different from my classmate.
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  I think my career which is just the start, finished my PhD
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  training and direct go to the industrial.
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  I first, my first job is to join the GSK and the China and
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  further pursue my research on T cell differentiations in
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  autoimmune conditions. But it's from the different
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  angles. It's for the drug development
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  with screening small molecules which could be suppress the T
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  cell activities and we will promote the T activities.
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  We want to control, control the autoimmune progressions in
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  multiple sclerosis, which is neuroinflammation disease and
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  also rheumatoid psoriatics with, you know, with the outing
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  inflammations in the in the joint and after in GSK for
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  almost 7 years, which I really learned how to develop an
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  innovative drugs in the in the outing settings.
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  So back to the 2015, I got an opportunity to as a entrepreneur
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  to sell biotech in China and the starting from the the companies
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  called IMAP and that's really fantastic opportunities because
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  2015 is the starting of you know the immunotherapies year because
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  the approval for PD1 antibodies such as Keytruda and Optivo.
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  So we worked as a map at that time.
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  We're focusing on the new generation e-mail checkpoint
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  development for example, like in CD37, like in CD 73, we are
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  seeking for another PD one on the road for the development.
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  Beside of that I think it is more related to today's we come
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  back to the 2015 we're starting for the bispecific development
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  and here our initial rationale is that there were no bispecific
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  e-mail checkpoint combination will have to resolve the re
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  refractory or UN responder for PD1 immune therapies.
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  There are developed the first time I I joined the Tsung
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  engaged development based on the full one BB based bispecific.
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  Yeah, IMF there at MMAP and ABL bio now it's a a Co stock list.
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  The company together we developed the four one BB based
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  platforms. Another I think it is more
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  related today is calling based 41 BB.
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  At that time, we find the four one BB based bispecific can
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  solve problems of four one BB, which in the past the four one
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  BB has shown the very severe liver tacticities and to which
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  can block its further explorations on ultimate
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  condition in in the liver with the severe liver tox and.
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  However, by using the bispecific and we can precisely control the
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  activation of four MBB which only happens on the in the tumor
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  because one only binds one arm bind to the tumor the other by
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  casting and they then for one they become deactivated.
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  So we can precisely control the the tissue activation which is
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  far from the liver. So in that the case, you can
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  make the in the tumor the four one BB activated and in the
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  without liver toxicity. So that is very smart designs
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  and recently these molecules we call them Chiva show very good
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  advocacies in the in the gastric cancers in the first one and
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  which come back to the 2020 we where M AB was listed on the
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  NASDAQ. I just wanted to pursue a new
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  career at that time the chairman of Lupu Bio Pharma, which is
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  listed on the Hong Kong exchange invite me to join the Lupu as a
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  head of research. So that's easier.
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  I joined Liverpool as a as a private space and as a senior
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  leaders, we lead the Liverpool biopharma list in Hong Kong.
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  And before, before I leave Liverpool 2020, before I leave
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  Liverpool 2025, they become a really biopharma company in
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  China. So I look at the local
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  biopharma. I also participate in the lead a
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  lot of ADC development. And we I also drive the two
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  person class ADC, one is TPC, three ADC and another is the Cdr
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  17. Basically ADC move, bring them
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  to the to the clinic and then in parallel for to further pursue
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  my interest in the career in the T cell engagers.
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  I find that in the four one BB, there's some limitations when I
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  go for the more with cosmic cold tumor, that means there's almost
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  no T cell infiltration situations.
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  The four one BB doesn't work well.
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  So and the further explorations we find when you bring the CD 3
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  and the four one BB together, we can do it.
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  So I incubate that platforms in the Liverpool biopharma and
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  which is likely which come back to the end of 2024.
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  We have opportunities because the the local biopharma wanted
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  more focus on their development of ADC and because there is one
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  PD one approving China, the second is a eufr based ADC
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  already approved in China, one or two focusing ADC and and the
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  PD 1. So I have an opportunity to
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  taking out the TCe and related the TCe platform out.
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  So at that time I call for my partner Jalen.
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  I just a call, I know Jalen, we know, I know Jalen is when IMAP,
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  he was the first CFO of IMAP and bring the I'm up to the next to
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  the NASDAQ. So I give him a call.
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  We have a hot pot dinner. So and then we decided to do it
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  together. So we are lucky ones when they
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  get to the opportunity to to to get a financing and also to
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  bring the leading asset out and also related to CD3's platforms
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  out. And there is where started from
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  Excel point. We finish that deals about $41
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  million financing at the August of 2025 S after very quick you
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  know, you know, development of our progress of our of our
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  programs and also our our platforms.
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  So we get a very quick follow on after six months later, so
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  almost at the end of 2024 earlier 2026 because pass around
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  it's about $27.7 million. So it's in total it's almost
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  reaching the six $8 million. So we have, you know, very good
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  positions to further develop the T cell engages in solid tumors
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  and in more specific autoimmune conditions.
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  So that's where the startings of Excel point.
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  Fantastic. Thank you.
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  Thank you for that overview. And yeah, like you said, you,
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  you launched with, you know, one of the largest seed financing
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  for for Chinese biotech for people that are less familiar
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  with with the company. Talk us through Excalar Point
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  Science in a little bit more detail.
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  When what gap did you believe existed in the T T cell engager
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  and immunology, you know landscape that you know made you
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  really start Excalar point? So that is for the T cell
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  engagers is a long journey. It's not just what something
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  started the 2010 file which come back to the 2014 I mean almost
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  more than 10 years ago. It's the first T cell engagers
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  Blencia only the CD 19 CDC have been approved, but it is going a
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  long way until the 20 222027 a first wave of T sign engagers
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  have been approved, which is almost on the hemidopole cancer
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  like in CD20 PCMA related T sign gauge approval in in DLPCR and
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  etcetera. However and the I think the
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  milestone event was the the first half of 2024 that the
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  first DL3 CD three that is the first T cell engages have been
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  approved in solid tumors. I think for the T cell
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  immunotherapy that's a real milestones for several reasons.
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  For the first one that is the first immune therapies have been
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  approved. The efficacious that in the past
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  was PD 1, you know, not less effective tumor site and the
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  first immunotherapy approved under PD1 relapse conditions
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  because you know there's no e-mail service have been
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  demonstrated after PB 1. And I think that the second
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  thing is that this trial is this is a benchmark.
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  Tell us, you know, what's the you know, the features of
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  functional design gaugers that is, you know, the new need of
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  first clean tumor social antigens and there is there is,
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  you know, this applications profile is like in the response
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  rate is now sold as high as at ADC.
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  You know, 50 or 7060% of the response rate is only 40% of
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  response rate. However, the peer the OS benefit
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  is very, very significant almost reach 14 months.
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  So moderate response rate and KB can be applications after PD1
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  and you know, very long OS. So this is set up a very good
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  standards and a good, you know, role models how he saw engaging
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  solid. However, currently you can see
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  the car teeth not going so well, but the T cell engagers coming
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  coming out. So that's I think the the that
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  really draw a lot of attentions by the investors by whole field
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  to know it's time for solid tuners.
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  I think for us is, is that we wanted to, you know, to to we
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  can do better. What's the next making the
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  better T sound engagers when coming to the CD 3 alone.
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  And I think another milestone that is because recently for the
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  T sound engagers field move into immune reset settings by using T
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  cell engages in autoimmune conditions.
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  We see a lot of you know, car tease.
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  We this will also happen on the 2024.
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  So peace allow this. That's trials that's cases.
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  We will let us know the T cell engages can be, you know,
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  working on autoimmune conditions, making a whole
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  immune reset. That means the research of holy
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  B cell immune reptile by making self reactive base off into
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  truly naive and and for second of cure, you know for cure for
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  six months or even longer. So that is also tremendous.
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  I think that's why T sign engagers do try draw a lot of
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  attentions on that for external point for the solid tumors.
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  We wanted to expand the we have pipelines to expand T sign
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  engagers not only for small salon, we want to we have
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  expansion to the Pine GI cancers is our second pipelines.
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  We want to make him into the clinic at the end of this year.
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  And then we also have a prostate cancers.
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  We also have you know, even though non small cell lung
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  cancers in the past, we're making T sign get can benefit
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  more. But the different the things are
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  different, it's more difficult that is, you know, the different
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  indications the you'll need a different kind of T cell
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  engagers. We wanted we wanted to not only
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  CD3 we under the CD3 plus. So we added the Co Stimu signals
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  as a as a full one BB to which could benefit the with the very
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  few that T cell efficiency in the cultural situations like in
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  CRC like in like even cold population in the small salon
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  and also in the past the steep, you know, prostate cancers is
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  supposed to be very cold tumor type.
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  The PD one even not proving these indications.
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  And that's our visions for for for the tissue and getting solid
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  tumors and how another thing is for the autoimmune conditions.
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  Our rationale is a little bit in the past they, they do the whole
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  piece of depletion and even reset for the new one.
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  And we wanted to be a more precisely to depletion only
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  pathogenic results. We wanted to precisely control
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  yet in that in that situations we can move the piece of
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  depletion strategy to other less severe autoimmune conditions for
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  you like maybe Sjogren's syndrome, maybe other you know,
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  B cell related autoimmune diseases not use lisal or lab
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  threaten like in SLE, like in terminal s s system siculosis.
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  This kind of indications we want to just move to using only
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  depletion for pathogenic B cells.
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  So that's this is making Excel point could, could, could be
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  differentiate. We wanted to to be
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  differentiated in the ultimate and and and solid humours.
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  No, absolutely. And since you've launched as
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  well you've you know, rapidly built these platforms,
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  progressed the six programs in a, you know, very short amount
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  of time. What's being key for you to
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  executing, you know at that speed and you know, while making
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  sure the quality and decision making has been so effective?
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  I think the based on three aspects.
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  The first aspect I think for the I just I just mentioned that the
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  T cell immune therapy as ATCT cell engager as a so T cell
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  immune therapy in the in autoimmune for the science part
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  is having demonstrate we don't worry about science.
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  I just we just need to better precisely control how you
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  control the T cell and to kill a target and make it more clean.
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  So what we need is for engineering, good engineering,
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  it's not easy. So the first you have the
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  certain the road is clear, you just need to the T cells.
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  I think the second is we have very good basis because we have
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  you know a lot of molecular tools like in we have ACD 3
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  sequencing ready, we have US coasting molecules or they're
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  already ready like in for one BB even though we have pursue other
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  costing like in CD 2. So in that case, because the Co
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  rationale that I called my first principle, first principle of T
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  sign engager field is how to using multi specific antibodies
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  to reconstitute immunologic synapse as natural as we could.
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  So you can you can you go when you zoom in the key molecules in
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  the immunologic synapse, there's a CD3, there is a cosine for one
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  BB we have there's just CD2 also we have this is it.
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  That means the answer is also you need you how to dissolve
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  resolve the problems in by protein engineer.
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  So that's only engineering things.
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  I think for the shoulder layer, you should worry understanding
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  the biology of the you know, the indications.
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  We we explore the different indications based on the
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  different indications on the on the T cells.
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  We apply the different you know, sometimes we're using for one
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  baby, sometimes we're using CD2 is based on dependent tumor T
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  cell in condition for using that.
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  And for the even though I think for the for the for the B cell
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  depletions, we only apply to CD3.
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  We didn't, we didn't using cocin because we just wanted to T cell
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  kill the B cell and we don't want to persist the T cell
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  activated because you know, ultimate conditions you you kill
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  the B cell, but you don't want to promote the T cell to other
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  ultimate conditions. That's that's why we quit
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  because we all the molecule to molecular tubes, we are already
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  enhanced and we based on the different indications we tailor
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  made the different, you know, molecules on that.
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  I think for the third all because all these things in the
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  clinic, we don't know we, but we have the the luxury because in
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  in we can apply both the in China and the US clinic
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  resources. It's possibly in the China there
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  are huge a mathematically large patient population needed to be
• 19:58
  treated. So in that case, we can do quick
• 20:02
  clinical to see we can come for 10 people or tons of people.
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  Patient data to tell us whether is this design is right or not
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  because in the past we already developed a very deep know how
• 20:19
  to molecule design and how this performance in the Sino.
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  Currently, we also have initially clinical radar.
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  We we build up, you know, this kind of algorithm, but this is
• 20:30
  in mind human algorithm to to build to quick build up, you
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  know, T sign engaged in the clinic.
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  So for the second program server program, we are more quick
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  because we have that. And I think for the last
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  currently we are also working with AI with agents.
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  We wanted to translate our knowledge of the TESAR engager
• 20:54
  to to to to AI and then AI back to help us to more quick to
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  design the next generation T sound engagers.
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  Before example, I will give you example our first T sound
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  engagers. We almost spend three years to
• 21:13
  make the molecules in the clinic based on our definitely know how
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  can we only use 11 months to make our prostate cancer
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  programs into the clinic. We shorten because we have two
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  ready and we have you know how to design and we get the quick
• 21:38
  answers from the Sino data and isn't got the quick design.
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  We know which range that could be successful in the human.
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  I think maybe in the future by using AI, maybe we can get more
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  quick design on the T sign engagers based on that one.
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  That's why I think I have a confidence excellent point.
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  Make a better drive in the in the clinic, yeah.
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  Now that makes sense and leave built the company up, you know,
• 22:05
  very quickly. You've got funding behind you
• 22:07
  just quickly. Before we finish, what's the
• 22:09
  plan now for you and Excalar Point over the next 12 months?
• 22:14
  That is because of the very well we're very looking forward we
• 22:20
  would we have we could achieve the first.
• 22:23
  We just wanted to further just explore what our initial TSR
• 22:30
  engaged CD3 Co team design, what's the safety and what's the
• 22:35
  potential efficacious and what's the dose in the human as the
• 22:39
  first things. And from that clinical data, we
• 22:42
  can really learn a lot is we, because we are the first one to
• 22:48
  design the CD 3 and the costing for one BB in C-section.
• 22:53
  That means in the working on simultaneous one because in the
• 22:58
  past, a lot of people working on in the combo because two
• 23:01
  bispecific signals in the combo situations you sometimes we they
• 23:06
  don't have other smart designs. They, they, they bind to CV3,
• 23:10
  but not for one baby. The bind for one be done not CV
• 23:13
  three. You are you are regional combo,
• 23:16
  but we are the first one to design they're working together,
• 23:19
  which more mimic the natural pizza activations.
• 23:23
  And I think this is the first one to to try them in human and
• 23:28
  we would we can learn that and we will accelerate our next, you
• 23:34
  know, new acting CD to new molecule design because we we
• 23:38
  learn we could achieve this. This kind of design can be
• 23:42
  potential safety may even though that that how is performance in
• 23:48
  human. It's what's what I'm really
• 23:49
  looking for what happened on the next we are also moving forward
• 23:57
  you know to push our prostate cancer and also our precisely be
• 24:03
  a pathogenic piece of depletion approach.
• 24:06
  I think maybe we can expect to these molecules into clinic
• 24:12
  maybe at the second-half of 2027 in that we will have more
• 24:18
  answers on our you know waiting molecule design and you know
• 24:22
  which can help on the patient worldwidely.
• 24:27
  Fantastic. Look, it's been a great story.
• 24:31
  Thank you so much for sharing a little bit about your career and
• 24:34
  everything around Escala Point. Everyone listening is going to
• 24:37
  be a really excited watching you guys over the next 12 months.
• 24:40
  So, Lee, thank you so much for coming on the podcast.
• 24:44
  And I look forward to, you know, seeing how everything goes over
• 24:47
  the next few few months and yeah, later on in the year.
• 24:51
  Yeah, thanks. It's a great talk.
• 24:53
  And then we wanted to share more stories in the future.
• 24:56
  Yeah, absolutely. Thank you, Lee.