BlossomHill Therapeutics, Inc. (BLSM) September 15, 2026 Conference Transcript

Welcome to our next Fireside Chat. I'm Robert Burns, the Managing Director of Senior Biotech Analysis at Suera. I'm joined today by Gene Kui, the CEO of the newly formed Blossom Hill, which just IPO'd. Gene, thank you for joining us today.

Thank you for having us here.

No problem. So I guess let's start from the 10,000 foot view. Considering that you just IPO'd in August, maybe for those who may be unfamiliar with the Blossom Hill story, tell us a little bit about the company and its pipeline.

Thank you. Yeah, I'm Jing Cui and the scientific founder and also president and CEO of Brossom Hill Therapeutics. And Brossom Hill Therapeutics was founded in June 2020, just in the middle of the pandemic, COVID-19 pandemic. And so stay at home and have, you know, kind of a really extra time and to really think about the science and because every company and funded and really need to have the directions and what exactly what we should do and what is our capability be able to solve and you know and high-end medical needs especially the needs needs the innovation of the chemistry and by training i'm the chemist and so this is why and kind of we really want to fund the clinic and mathematical need the chemistry innovation and with the strong support of the leading investors and we have built you know kind of very strong and uh you know kind of the uh we have built a very strong leadership team and also the and the advanced two molecules and micro sexually molecule and into clinic and also one and in the IND enabling studies. And as a candidate, as a founder, and we have built up all our pipelines from the ground up and from identifying our medical needs. And so here's the summary, the blossom heal way to deliver our candidates and identify our medical needs for patients. So this is definitely, and we want to really kind of identify something and might be stuck, you know, kind of quite difficult in the field and then using the you know analyze and you know what is the issue there and how we can solve the issues from which angle and so the different part you know we have to the you know kind of do the structure based design however and different from structure based design here we really focus on the proton dynamics because in the disease state and the protein probably stay in a different conformation at which state is better to overcome. The first therapy requirement probably is different compared to resistance setting there. And then, you know, need optimization and to identify and the clinical and the candidates there. So this is, you know, and our pipeline and we have only ECFI inhibitor and this is a microsecreted molecule. We will talk more about this molecule and have the broad inhibition against the classical ECFR mutation, atypical mutation. And also most important, be able to tackle all of these resistant mutations and currently in the late and the expansion and the stage. And we hope to have for the end of the phase five meeting and in the Q4, 2026. And the CLK inhibitor is a target and a broad resistant mechanism associated cancer treatment. We know the cancer treatment, the ultimate goal is to shrink the tumor. And then shrink the tumor will generate common resistant mechanism and the scape and to for the survivor, and also most important DNA damage repair pathway. CLK is modulate and the certain aging reach the splicing protein and then leading to the modulate and the end result is a modulate DNA repair pathway and also survival and the balance there and this this project currently in the dose escalation in both monotherapy and also in combination and with vanilla clout and now our pancreas inhibitor and have the novel and the chemicals design and leading to very distinctly different profile and with a pseudo irreversible characteristic and this molecule and in the late imd enabling studies and we plan for imd summation and in the first half and the

first quarter 2027. thanks jean uh so you know similar to what we saw with your prior company turning point therapeutics there seems to be a recurring theme here when you when we look at approach you took when designing blossom hills drug candidates uh in particular two of the two of the three of your of your assets are macrocyclic based structures maybe you know help investors who might not be as scientifically inclined understand the rationale between this and the advantages that macrocyclic based inhibitors actually possess over non-macrocyclic based ones Yeah, great question.

And so kind of for the, so that is, you know, kind of for the, my first design for microcyclic and from Rolatinib and later and reprotectinib. So microcyclic design is a common tool for medicinal chemists to solve the issues. And quite often by the end, microcyclic and quite often will deliver and a super cell, super potency and good drug-like properties and also you know kind of holds a good safety profile and the bottom line you know microcyclic is to rigidify the conformation to have the precise interaction with the protein there and so kind of the not all of the target and will suitable for the microcyclic design such a keras and a switch to pocketing paper may not good for the microcyclic however when we work on kinase and especially for resistant patient population and this is really kind of the two we have to use so when we're talking about the resistant and the kind of you know the kinase already and the the pathway is a highly activated and you know developer resistant as the later generation and they need to overcome the resistance that is number one requirement And also, the molecule needs to be also super better potency against the primary mutation. We know that different subclones of primary and mutations still exist, co-existed, either cis or trans, and we resist the mutation. Therefore, you know, the molecule needs to be significantly better than previous generation, be able to overcome all of this resistance. and so and also you know kind of to avoid other and mutations so that is why and for the kinase and next generation when we design the molecule target atp center need to achieve the super potency the micro cycle is the you know the best tool to use and as you can see both of the and and the design i designed both of our aptly protect anyway as the micro cycle you can see and the you know small cycle the microcyclic there and be able to achieve both the supercell potency against the primary mutation and also most important is resistant mutation and good pk properties enables the molecule to overcome resistance in the later line and also why it used to the front line and achieve you know make the treatment outcome significant beep like relapne using to the frontline. And it has improved the PFS from original and the crescent in less than one year to over seven years. So this is what we target to. And then you know, kind of the pandemic, I'm think about the easier file. So easier file and see some nice someone asking, you know, already three generation EGFI inhibitor has been approved. And you know, Tagrezo is the the third generation covalent irreversible molecule. So this one, and the, you know, here is shows that, you know, the structure there. And so the osmortinib is, the chemical structure is not really the true binding for the ECFR protein there. Without the covalent binding part, I highlight there is a blue color to form the covalent binding there. And without the covalent, that will be submicromolar activity there. And to, you know, kind of overcome this C797S, the molecule design has to be a non-covalent molecule, and also need to capture the true and the protein characteristic of the easier farm. And so we designed a novel microcyclic structure, and after, you know, kind of this structure I could design, and as you compare the first generation and the third generation, and this structure not share any of the commonality with them. And so after this optimization, we are able to achieve the supercell protein subnanomolar against the classic atypical mutation. The brown color, and that is a compound resistant mutation, as you can see, it is equal potent against them. This is very important when we use it in the later than there. The molecule is also and the tenfold more potent compared to covalent molecule or smudging it there. And this is also the only molecule and be able to achieve this broader activity against the both primary and resistant mutation and have a great selectivity window over the wild type ECF.

Awesome. Thank you for that background. You know, with that as the backdrop here, you know, you presented some data at WCLC literally a few hours ago. Maybe you could walk us through that data for your lead agent BH3064.3. And what stood out to you most from from that data set?

Yes, kind of for people who don't know the data, let me kind of present that here is kind of updated in the WCLC and we updated our first month and the data for patients with system nice, someone has resistant population. As you remember, we first present the data at ASCO and 2026 and with the patient, efficacy available patient and it's about 34 patients there. And in the WCLC and our data card is May 12th and the 2026 with efficacy and the follow-up until August and 10, 2026. And the medium follow-up time is 6.9 months. And this time we present 40 patients and it's an efficacy available patient and the object response rate, and it's a 45%. And the reason that is 17 patient is a conformed response. We have one patient is an unconfirmed response ongoing, waiting to be conformed. And the disease control rate, and it's 88%. And so that is a kind of the, and the patient, as you can see, the ways and the results and the T790M, and it shows a great efficacy there. And also, and with the patient treated without chemotherapy, and ORR is 53%, and with the chemotherapy is 38% there. And so the patient, and actually the, and it is a highly kind of brain penetrated, about over 50% patient have the brain and the metastasis there. So the data also kind of a very important update, and it is a kind of a durability. This is the very first thing, you know, and the molecule demonstrate a durable response against C7971S. And here, and, you know, with the 6.9 months and a follow-up, and the 63 patients still remain unsteady. As you can see, we have both three patient treatment and already beyond one year. So that is, you know, kind of for everybody and waiting for the data to see the C7971S still oncogene driver and be able to achieve a durable response. At the same time we also update on the safety profile at efficacy level and in the expansion dose level and we have three dose level in the expansion cohort at 40 meg and 50 meg and also 60 meg BID dose level and 174 patient there. As you can see, the dose reduction rate is low, it's 9%, and also, and this continued rate is 3%, and related treatment rate is AEs there. EZFR, well-type related AEs, and mainly, and it's a great one. You can see both the rash and also diarrhea, and and it is, most of them is a greater one. And the molecule and also, and it is have the rare pneumonitis and only about a 1%, we only have two case there and possibly related molecule and no clinically significant treatment related cardio effect such as QTC elongation. And among them, all of the AEs, the most common AE and the TR-AE is the bilirubin increase. So this bilirubin increase and it's due to a 643 inhibit and transfer to UGT1A1. So the transfer UGT1A1 enzyme responsible for the gluconeidation of the bilirubin. Therefore, what we observed the bilirubin increase mainly is unconstructed and no symptom associated with patient and quite often no need for the doser and adjustment. And it's kind of a greater sleep, and it's about 7% among the 174 patients. We also observed some of ALT, AST elevation, and it is about 7% for the ALT. These two, ALT and the AST, and also compared to the bilirubin, have the different mechanism. And the bilirubin increase quite often. is unsight quick and when we reach the steady state and it is, you know, we can observe that and then, you know, and the liver enzyme increase and quite often kick in and in about six weeks there. And so this is two different mechanisms and no case and means that his loss there.

Thank you for that. So, you know, one of the things that we're also seeing within the field is from a competitive landscape perspective. Obviously, we've seen some data from Hansho Pharma, Dissol, as well as Voronoi. So how are you interpreting those competitive data sets and where do you think 3064.3 is potentially differentiated relative to those competitor agents?

Yeah, so we are glad to see the three companies and try to solve the C7971S issue there. C797 as first reported, you know, back to 10 years ago, 2015, and now we finally see it's able to overcome and release resistance. And all of the molecules are in the early phase one stage, and we don't know too much about the structure of the other three molecules. And based on the rare molecule, and it is claimed and based on the corporate presentation, and it is a generation and, you know, first generation and a modification and it is not able to overcome and T790M resistant. And then for other two, we don't know exactly the structure based on the preclinic data and likely, you know, kind of look like and against the potency, against the primary mutation, maybe, you know, kind of not equal potent compared to osmortinib or less potent And we do believe it is very important and kind of for the next generation needs to be significant, more potent compared to previous generation osmertinib there. So we compare with the public information, we do believe, and 643 is the only molecule have tenfold more potent compared to osmertinib, equal potent against all of these resistant mutations and also atypical mutation. it also have good activity against Exxon 20, good selectivity window. And since it is a micro-secret design, and we have a very good PK exposure level, and it makes the clinic coverage and probably gives the great advantage and to give, as you can see, the durable response there.

Awesome. Thank you for that. Why don't we shift gears now to a few of the other assets in your pipeline. I wanted to focus on your RAS inhibitor, 50-21-84. You know, obviously we saw recently Diraxxon RAS that being FDA approved or gaining FDA approval in metastatic PDAC. And, you know, there are a number of other pan-RAS or pan-K-RAS approaches that are moving through development. What specifically differentiates your approach and how are you thinking about the development strategy for this agent?

Yes, the pan-RAS inhibitor really revolution and in the PDAC. And so we also know the history of the targeted therapy, the first one and represent the start of the new era. And then, you know, for the next late comer and need to really focus on the improvement, how we can make the treatment go to the next level and both on safety and the most important and it's efficacy and the durability, how we can be able to achieve the treatment and beyond the one year and the two year and then the time of treatment duration there. So the kind of the other molecule and the 501284 is a novel chemical structure and the designed is a switch two inhibitor. I want to have a little bit of background regarding to the distinguishing, kind of a different from the switch two inhibitor compared to the tricomplex molecule. So the tricomplex molecule we know is an onstage inhibitor. And it is a block and uses direct hindrance from the cyclofilling block, you know, and rough and a factor coming into active is a Keras. And however, this tri complex also facilitates and the GTP and hydrolysis back to the GDP, and then GDP will cycle back and to the GTP. So that means it is not a shutdown for cycling, and with the second continue, and that will be the issue for the durability. And then the for the switch to pocketing inhibitor, it is in to rigidify the KRAS protein makes the surface is no longer to be flexible enough to have tight interaction with a factor such as a draft of the, you know, kind of the GTP, GTP, you know, that's a GF, you know, and as all as one, you know, this kind of effector. So it is completely shut down the cycling there. And we know the clear on the molecule, the next generation achieved the progression free surviving time more than one year. And to leverage it through, you know, this is success, we design our molecule as a pseudo-adversible molecule, be able to completely shut down and rust and rough interactions and achieve the significantly deeper and longer in the available study compared to tricomplex molecule.

Awesome, thank you for that. You know, one of the potential interesting aspects of Blossom Hill is that, you know, you've got multiple programs in-house, you know, under one roof, and there's the potential for internal combinations, at least in my opinion. So where do you see opportunities to combine your pan-K-RAS agent with other agents within the Blossom Hill portfolio? And what combinations do you find most compelling?

The internal combination and definitely our cell-K inhibitor, and it is a target, you know, kind of a general and a resistant mechanism, and especially apoptosis pathway and DNA repair pathway. And so it is, you know, kind of in our preclinical data, data, and it shows a great synergy when it's combined with the ECF-5 inhibitor or combined with the KRAS inhibitor, where people don't know the splicing and the modulation, and you're probably very familiar with the recent exciting days, the PRMT-5 and inhibitor combination with the KRAS in a great synergy there. And this modulates the spicing in certain point and have a similar outcome compared to PRMT5. And the preclinical data is very exciting.

So, you know, I'm pretty sure you're referring to the TANGO data set where, you know, they combine their PRMT5 with the PAN-K-RAS, Daraxon-RAS. Have you shown any data preclinically that compared the TANGO agent with Daraxon-RAS compared to your CLK inhibitor plus your PAN-K-RAS inhibitor? yes and this is a great question and this is really experiment ongoing okay and we hope we'll present more data as the coming and the next year asia oh perfect perfect so we're running up with time one last question if i may uh maybe to wrap things up you know as we look towards the next 12 to 18 months what sort of key catalyst can investors look forward to yeah for our omni eCFR project and the immediate and catalyst and the milestone and it's the end of the phase one

meeting and that is coming and the q4 and the 2026 and that will identify and get agreement based on the opportunity selection and also the pivotal and phase two design and for c797 as resistant population and the next year and the uh 2027 first half will present more data on C797S, especially, and we hope we can read out the durability and for this. And we also present some data before and regarding naive patient. And the second half, 2027, we'll present more data on the naive patient and hope we can read out at least one year durability for TK and naive patient population. And also, and we already start in combination with the chemotherapy, and we will present a second half 2027 and we will present a combined initial baseline data combination with chemotherapy 643 and in terms of safety and also anti-tumor activities.

Awesome, thank you, Ching, for joining us today. I'm looking forward to all the data sets that are going to be coming up from Blossom Health.

Thank you.