Welcome to our next fireside chat. I am Robert Burns, the managing director at H.C. Wainwright. I am joined today by Jean Cui, the CEO of the newly formed BlossomHill, which just IPO. Jean, thank you for joining us today. Thank you for having us here. No problem. I guess let's start from the 10,000 ft view. Considering that you just IPO in August, maybe for those who may be unfamiliar with the BlossomHill story, tell us a little bit about the company, and its pipeline. Thank you. I am Jean Cui, and the scientific founder and also president and CEO of BlossomHill Therapeutics. BlossomHill Therapeutics was founded in June 2020, just in the middle of the COVID-19 pandemic. Stay at home and have, kind of a real extra time and to really think about the science and because every company founded really need to have the directions and what exactly what we should do and what is our capability be able to solve high unmet medical needs, especially the needs the innovation of the chemistry. By training, I am the chemist and this is why, kind of, we really want to fund the clinic and medical need, needs the chemistry innovation. With the strong support of the leading investors, we have built a very strong leadership team and advanced the two macrocyclic molecules into clinic, and also one in the IND-enabling studies. As a chemist, as a founder, we have built up all of our pipelines from the ground up, from identify unmet medical needs. Here is the summary, the BlossomHill way to deliver our candidates and identify unmet medical needs for patients. This is definitely, we want to really identify something might be stuck, quite difficult in the field. Then using the analyzing what is the issue there, and how we can solve the issues from which angle. The different part, we have to do the structure-based design. However, different from structure-based design, here, we really focus on the protein dynamics because in the disease state the protein probably stay in a different confirmation at which state is better to overcome. The first line of therapy requirement probably is different compared to resistant setting there. Then, lead optimization to identify the clinic candidates there. This is our pipeline, and we have only EGFR inhibitor, and this is a macrocyclic molecule. We will talk more about this molecule. It has the broad inhibition against the classical EGFR mutation, atypical mutation, and also most important, be able to tackle all of these resistant mutations and currently in the late expansion stage. We hope to have the end of the phase I meeting in Q4 2026. 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 escape for the survival, and also most important, DNA damage repair pathway. CLK is modulated the serine/arginine-rich splicing protein, and then leading to the modulate, and the end result is a modulated DNA repair pathway and also survival balance there. This project currently in the dose escalation in both monotherapy and also in combination with venetoclax. Then our pan-KRAS inhibitor has the novel chemical design leading to very distinctly different profile with a pseudo-irreversible characteristic. This molecule in the late IND-enabling studies, and we plan for IND submission in the first half, first quarter 2027. Thanks, Jean. Similar to what we saw with your prior company, Turning Point Therapeutics, there seems to be a recurring theme here when we look at the approach you took when designing BlossomHill's drug candidates. In particular, two of the three of your assets are macrocyclic-based structures. Maybe, 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. That is kind of my first design for macrocyclic and from lorlatinib and later and repotrectinib. Macrocyclic design is a common tool for medicinal chemists to solve the issues. Quite often by the end, macrocyclic will deliver super cell, super potency and good drug-like properties and also, kind of the good safety profile. The bottom line, macrocyclic is rigidify the confirmation to have the precise interaction with the protein there. Not all of the target are suitable for the macrocyclic design, such as KRAS and Switch-II pocket inhibitor may not good for the macrocyclic. However, when we work on the kinase, and especially for resistant patient population, this is really the tool we have to use. When we are talking about the resistant and the kinase already and the pathway is highly activated and develop resistant as a later generation, the need to overcome the resistant, that is number one requirement. Also the molecule needs to be also super better potency against the primary mutation. We know that different sub-clones of primary and mutation still co-existed, either cis or trans, with the resistant mutation. Therefore, the molecule need to be significant better than previous generation, be able to overcome all of this resistance. Also, to aware other mutations. That is why, for the kinase and next generation, when we design the molecule target ATP center, need to achieve the super potency, the macrocyclic is the best tool to use. As you can see, I designed both lorlatinib, repotrectinib as the macrocyclic. You can see, the small cycle, the macrocyclic there. Be able to achieve both the super cell 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. Also when it used to the front line and make the treatment outcome significantly, like lorlatinib used into the front line. It has improved the PFS from original crizotinib less than one year to over seven years. This is what we target to. Then, during the pandemic, I was think about EGFR. EGFR and the C797S. Already third generation EGFR inhibitor has been approved, and Tagrisso is the third generation covalent irreversible molecule. This one here it shows Tagrisso's structure there. The osimertinib, the chemical structure is not really the true binding for the EGFR protein there. Without the covalent binding part, I highlight there is a blue color to form the covalent binding there. Without the covalent, that will be submicromolar activity there. To overcome the C797S, the molecule design have to be a non-covalent molecule, and also need to capture the true and binding the protein characteristic of the EGFR. We designed a novel macrocyclic structure, and after this structure I could design, as you compare the first generation and the third generation, this structure not share any of the commonality with them. After this optimization, we are able to achieve the super cell potent subnanomolar against the classic ATCC mutation, the brown color, that is a compound-resistant mutation. As you can see, it is equipotent against them. This is very important when we use it in the later then there. The molecule is also tenfold more potent compared to covalent molecule osimertinib there. This is also the only molecule be able to achieve this broader activity against both primary and resistant mutation, and have a greater selectivity window over the wild type EGFR. Awesome. Thank you for that background. With that as the backdrop here, you presented some data at WCLC literally a few hours ago. Maybe you could walk us through that data for your lead agent, BH-30643. What stood out to you most from that data set? Yes. For people who don't know the data, let me present. Here is updated in the WCLC, and we updated our first month data for patients with C797S resistant population. As you remember, we first present the data at ASCO 2026, with efficacy evaluable patient, it's about 34 patients there. In the WCLC, our data cut is May 12, 2026 with efficacy follow-up until August 10, 2026. The median follow-up time is 6.9 months. This time we present 40 patient, it's efficacy evaluable patient, object response rate, it's 45%. We think that is 17 patient is a confirmed response. We have one patient is unconfirmed, the response ongoing, waiting to be confirmed. The disease control rate is 88%. The patient, as you can see on the risk and the result and the T790M, it shows a great efficacy there. Also, with the patient treated without chemotherapy, ORR is 53%, and with the chemotherapy is 38% there. The patient actually is a highly brain penetrate. About over 50% patient have the brain metastasis there. The data also kind of a very important update, and it is kind of a durability. This is the very first thing, and the molecule demonstrate a durable response against C797S. Here, with the 6.9 months in a follow-up, 63 patients still remain on study. As you can see, we have those three patient treatment already beyond one year. That is, kind of for everybody waiting for the data to see the C797S is 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. We have three dose level in the expansion cohort at 40 mg, 50 mg, and also 60 mg BID dose level. 174 patient there. As you can see, the dose reduction rate is low, is at 9%, and also, discontinued rate is 3%, and treatment-related AE there. EGFR wild type related on AEs mainly is a grade 1, you can see both the rash and also diarrhea, and most of them is a grade 1. The molecule also it is have the rare pneumonitis and only about 1%, we only have two case there, and possibly related molecule. No clinically significant treatment-related cardio effect such as QTc elongation. Among all of the AEs, the most common AE and the TRAE is bilirubin increase. This bilirubin increase is due to, BH-30643 inhibit transporter UGT1A1. The transport UGT1A1 enzyme responsible for the glucuronidation of the bilirubin. Therefore, what we observed, the bilirubin increase mainly is uncomplicated and no symptom associated with patient, and quite often no need for the dose adjustment. There's kind of a grade 3, and it's about 7% in the amount of 174 patients. We also observed some of ALT, AST elevation, and it is in about 7% for the ALT. These two, ALT and AST, also compared to the bilirubin, have the different mechanism. The bilirubin increase quite often is onset quick, and when we reach the steady state, we can observe that. Then, the liver enzyme increase quite often kick in in about six weeks there. This is two different mechanism and no case missed his loss there. Thank you for that. So, 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 Hansoh Pharma, Daiichi Sankyo, as well as Voronoi. So, how are you interpreting those competitive data sets, and where do you think BH-30643 is potentially differentiated relative to those competitor agents? Yeah. So, we are glad to see the three company and follow, try to solve the C797S issue there. C797S first reported back to 10 years ago, 2015, and now we finally see is able to overcome and release resistant. All of the molecule is in the early phase I stage, and we don't know too much about the structure of the other three molecule. Based on the, w e are in molecule and it is a claim and based on the corporate presentation, and it is a generation and, first and the generation and the modification, and it is not able to overcome T790M resistant. For other two, we don't know exact structure based on the preclinical data and likely, kind of look like and against the potency, against the primary mutation, maybe, kind of not equal potent compared to osimertinib or less potent. We do believe it is very important and then, kind of the next generation needs to be significant, more potent compared to previous generation osimertinib there. So, we do compare with the public information. We do believe 643 is the only molecule have tenfold more potent compared to osimertinib, equal potent against all of these resistant mutation and also atypical mutation. It also have good activity against exon 20, good selectivity window. Since it is a macrocyclic design and we have the very good PK exposure level and makes the clinic coverage and probably give the great advantage and to give the, 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, BH-501284. Obviously, we saw recently daraxonrasib being FDA approved or gaining FDA approval in metastatic PDAC. There are a number of other pan-RAS or pan-KRAS approaches that are moving through development. What specifically differentiates your approach, and how are you thinking about the development strategy for this agent? Yeah. The pan-RAS inhibitor really revolution in the PDAC. We also know the history of the targeted therapy, the first one and represent the start of the new era. For the next latecomer, need to really focus on the improvement, how we can make the treatment go to the next level, both on safety and the most important, its efficacy and the durability, how we can be able to achieve the treatment beyond the oneb year and the two year, the time of treatment duration there. For the other molecule, BH-501284 is a novel chemical structure. The design is a Switch-II inhibitor. I want to have a little bit of background regarding to the distinction, kind of different from the Switch-II inhibitor compared to the tri-complex molecule. The tri-complex molecule we know is an on stage inhibitor. It is a block and uses steric hindrance from the cycle feeding block, and RAF and effector coming interact with the KRAS. However, this tri-complex also facilitate the GTP hydrolysis back to the GDP. GDP will cycle back to the GTP. That means it is not a shutdown for cycling. With the cycling continue, that will be the issue for the durability. For the Switch-II pocket inhibitor, it is rigidify the KRAS protein, makes the surface is no longer to be flexible enough to have tight interaction with effectors such as RAF or the GTP, GEF, and the SOS1, this kind of effector. It has completely shut down the cycling there. We know the KRAS G12C coordinate molecule, the next generation achieved the progression-free surviving time more than one year. To leverage this success, we design our molecule as a pseudo-irreversible molecule, be able to completely shut down RAS and RAF interactions and achieve the signaling deeper and longer in the in vivo study compared to tri-complex molecule. Awesome. Thank you for that. One of the potential interesting aspects of BlossomHill is that you've got multiple programs in-house under one roof. There's the potential for internal combinations, at least in my opinion. Where do you see opportunities to combine your pan-KRAS agent with other agents within the BlossomHill portfolio, and what combinations do you find most compelling? The internal combination and definitely our CLK inhibitor, it is a target, kind of a general and resistant mechanism, especially apoptosis pathway and DNA damage repair pathway. It is, kind of in our preclinical data, it shows a great synergy when it is combined with the EGFR inhibitor or combined with the KRAS inhibitor, where people do not know the splicing and kind of the splicing and modulation. You are probably very familiar with the recent exciting days, the PRMT5 inhibitor combination with the KRAS in the greater synergy there. This modulates the splicing in certain point and have the similar end outcome compared to PRMT5. The preclinical data is very exciting there. I am pretty sure you are referring to the Tango dataset where they combine- Yeah their PRMT5 with the pan-KRAS daraxonrasib. Have you shown any data preclinically that compared the Tango agent with daraxonrasib compared to your CLK inhibitor plus your pan-KRAS inhibitor? Mm-hmm. Yes, this is a great question, and this is really experiment ongoing. Okay. We hope we will present more data at the coming and the next year AACR. Oh, perfect. We are running up on time, one last question, if I may. Maybe to wrap things up, as we look towards the next 12- 18 months, what sort of key catalyst can investors look forward to? For our only EGFR project, the immediate catalyst and milestone is the end of the phase I meeting, that is coming in Q4 in 2026. We will identify and get agreement with the on [ash IIB] Inspection, and also the pivotal phase II design for C797S resistant population. Next year, in the 2027 first half, we will present more data on C797S especially, and we hope we can read out the durability for this. We also present some data before regarding naive patient. In the second half of 2027, we will present more data on the naive patient and hope we can read out at least one year durability for TKI-naive patient population. Also, we already start in combination with the chemotherapy, and we will present the second half 2027, and we will present initial phase I data combination with chemotherapy 643, in term of safety and also antitumor activities. Awesome. Thank you, Jean, for joining us today. I am looking forward to all the datasets that are going to be coming up from BlossomHill. Thank you.