Blossomhill Therapeutics, Inc. · NASDAQ:BLSM
Blossomhill Therapeutics — J.P. Morgan 2026 Healthcare Conference
25 slides from Blossomhill Therapeutics's conference presentation, January 2026
Slide 1: Company Overview
Company Overview J.P. Morgan 2026 Healthcare Conference THE NEXT LEAP FORWARD IN PRECISION MEDICINE
Slide 2: Intelligently designed small molecules
2 Intelligently designed small molecules to address the challenges of cancer treatment resistance with the potential for deeper, longer response $100M $84M $71M Preferred Series B CLK OMNI-EGFRTM Preferred Series B+ Preferred Series A Inhibitor Inhibitor (BH-30236) (BH-30643) Brahma Capital Founded
Slide 3: Experienced Leadership, Proven Drug Design Expertise
3 Experienced Leadership, Proven Drug Design Expertise J. Jean Cui, PhD 3 FDA-Approved Cancer Therapeutics Scientific Founder, President and CEO Scientific Founder, CSO of: AUGTYRO® LORBRENA® (repotrectinib) (lorlatinib) XALKORI® (crizotinib) Acquired ~$1Billion by BMS in 2022 Multi-$Billion annual
Slide 4: Our Differentiated, Global, Wholly-Owned Pipeline
4 Our Differentiated, Global, Wholly-Owned Pipeline Phase 1 Phase 1 IND Target Candidate Indication/Therapeutic Area Differentiation/Opportunity Discovery Dose Dose Enabling Escalation Expansion • Mutant-selective, non-covalent, macrocyclic OMNI-EGFR EGFR BH-30643 EGFR-mutant NSCLC inhibitor • Poten
Slide 5: BH-30643: OMNI-EGFR Inhibitor
5 BH-30643: OMNI-EGFRTM Inhibitor Novel macrocyclic, non-covalent, targeting mutant EGFR active conformation
Slide 6: Making a Leap in Patient Treatment Outcomes
6 Making a Leap in Patient Treatment Outcomes AC H I E V I N G LO N G E R P F S A N D P R E - E M P T I O N O F R E S I STA N C E W I T H S U P E R - P OT E N CY EML4-ALK Inhibitors in ALK+ NSCLC ROS1 Inhibitor in ROS1+ NSCLC 3rd Gen: 2nd Gen: Macrocyclic Lorlatinib Macrocyclic Repotrectinib Cell Po
Slide 7: Our Goal: Making the Leap in EGFR-mutant NSCLC
7 Our Goal: Making the Leap in EGFR-mutant NSCLC Limitations of Existing EGFR TKIs: • Suboptimal efficacy constrained by wildtype EGFR/HER2 toxicity • Liable to on-target resistance (e.g. T790M, C797S, etc.) Our Goal • Targeting only a subset of EGFR mutations (eg, classical, PACC, exon 3rd Gen: Osi
Slide 8: Existing EGFR Tyrosine Kinase Inhibitors Share Structure Similarities and Common Functional Liabilities
Existing EGFR Tyrosine Kinase Inhibitors Share Structure 8 Similarities and Common Functional Liabilities T790M-resistance C797S-resistance N O HN N N N N N H O Gefitinib Afatinib Osimertinib Lazertinib Newer EGFR inhibitors commonly iterate on prior designs, inheriting the same BDTX-1535 limitation
Slide 9: Existing EGFR Tyrosine Kinase Inhibitors Share Structure Similarities and Common Functional Liabilities
Existing EGFR Tyrosine Kinase Inhibitors Share Structure 9 Similarities and Common Functional Liabilities T790M-resistance C797S-resistance N O HN N N N N N H O Gefitinib Afatinib Osimertinib Lazertinib BDTX-1535 Firmonertinib Many TKIs use a back-pocket motif for potency Other TKIs covalently bind
Slide 10: Design Principle: Targeting the Mutant EGFR Active Conformation
10 Design Principle: Targeting the Mutant EGFR Active Conformation Wildtype EGFR Mutant EGFR adopts prefers an inactive, an active, closed open conformation conformation Targeting the active conformation unlocks the potential for OMNI-EGFR activity BLOSSOMHILL THERAPEUTICS AACR 2025
Slide 11: BH-30643 Represents a First-in-class OMNI-EGFR Kinase Inhibitor
11 BH-30643 Represents a First-in-class OMNI-EGFR Kinase Inhibitor Selectivity over 371 human WT kinases IC50 (nM): Median (N) Classical (N=15) Atypical (N=51) Ex20ins (N=34) Driver 0.60 (8) 0.81 (43) 4.73 (28) w/ C797S and/or T790M 0.43 (7) 0.63 (8) 3.69 (6) Note: Classical mutations include ex19de
Slide 12: Unique Design Overcomes the Limitations of Contemporary EGFR TKIs
12 Unique Design Overcomes the Limitations of Contemporary EGFR TKIs 10000 Classical Atypical BH-30643 has 3 distinguishing 1000 Inhibition IC50 (nM) features Cell Proliferation 100 1. Sub-nM potency against 50 nM 10 classical EGFR mutations: 10x more potent than osimertinib 1 2. Wide therapeutic wi
Slide 13: BH-30643: SOLARA Clinical Trial
13 BH-30643: SOLARA Clinical Trial Global Phase 1/2 study
Slide 14: EGFR-Mutant NSCLC Is a Prevalent Global Disease
14 EGFR-Mutant NSCLC Is a Prevalent Global Disease EGFR-mutant Patients Amivantamab & Ex20 chemo Afatinib Atypical Ins ORR 67% ORR 59% PFS 11.4m PFS 10.6m Ex19del On- Classic No drug effective No Target Osimertinib Resistance ORR 80% against all EGFR established PFS 18.9m targeted mutation subtypes;
Slide 15: BH-30643-01 (SOLARA) Global Phase 1/2 Clinical Trial
15 BH-30643-01 (SOLARA) Global Phase 1/2 Clinical Trial • Global Phase 1/2 trial • Enrollment initiated January 2025 • Now enrolling at >30 sites in 9 countries Countries with Active Sites Countries to be Activated BLOSSOMHILL THERAPEUTICS ASCO 2025, ENA 2025
Slide 16: BH-30643 PK Profile: High and Sustained Exposure
16 BH-30643 PK Profile: High and Sustained Exposure Exposures at doses ≥40 mg BID well exceed the Exposures at candidate dose levels exceed those target EC90 of many contemporary EGFR TKIs Steady state Cave (ng/mL) 1400 1200 1000 800 600 400 200 0 Paired with super-potency, high exposures could perm
Slide 17: Overcomes C797S Resistance Even in the Presence of T790M
17 Overcomes C797S Resistance Even in the Presence of T790M C797S & exon 19 deletion C797S & T790M & exon 19 deletion • 5 prior lines of therapy including osimertinib, • 8 prior lines of therapy including osimertinib, amivantamab, and IO investigational TKI, EGFR/met ab, ADC, etc • Partial response
Slide 18: Breadth of Activity Includes Brain Mets and Atypical EGFR Mutations
18 Breadth of Activity Includes Brain Mets and Atypical EGFR Mutations Exon 20 insertion with brain metastases L861Q (atypical) after multiple TKIs • 3 prior lines of chemotherapy • 4 prior lines including platinum, erlotinib, • Partial response sustained on multiple osimertinib, and chemo/mobocerti
Slide 19: SOLARA Expansion Cohorts: Now Enrolling Across Multiple Dose Levels
19 SOLARA Expansion Cohorts: Now Enrolling Across Multiple Dose Levels 6 Expansion Cohorts (n ~20-40 each): TKI Pretreated Cohorts 1) Classical mutation with C797S resistance 2) Atypical mutations after one prior TKI TKI-Naive Cohorts Potentially Escalation & 3) Classical mutations registrational ba
Slide 20: BH-30236: Macrocyclic CLK Inhibitor
20 BH-30236: Macrocyclic CLK Inhibitor Novel macrocyclic, non-covalent, targeting aberrant alternative splicing
Slide 21: Targeting Aberrant Alternative Splicing
21 Targeting Aberrant Alternative Splicing Addressing Aberrant Importance of Alternative Alternative Splicing Extends Importance of CLK Splicing the Targetable Proteome CLKs Exon Intron Exon SRSFs Exon Intron Exon • A single gene can produce multiple forms of a protein via • CDC-like kinases (CLKs)
Slide 22: Synergistic Effect of CLK Inhibition in AML Models
22 Synergistic Effect of CLK Inhibition in AML Models • Hematologic malignancies such as AML are especially dependent upon aberrant alternative splicing • In AML models, CLK inhibition with BH-30236 could overcome venetoclax resistance, even when dosed at low dose levels (6.25 mg QD of BH-30236, equ
Slide 23: BH-30236: On-going Phase 1 FIH Study in AML/HR-MDS
23 BH-30236: On-going Phase 1 FIH Study in AML/HR-MDS Objective: Evaluate safety & tolerability, identify doses for expansion • Monotherapy dose escalation on-going across multiple US sites • Now studying dose level 9, with no safety limitations seen with continuous daily dosing • Combination dose e
Slide 24: Making a Transformational Leap in Cancer Therapy
24 Making a Transformational Leap in Cancer Therapy
Slide 25: Intelligently Designed Molecules to Address the Challenges of Cancer Treatment Resistance
Intelligently Designed Molecules to Address the Challenges 25 of Cancer Treatment Resistance BH-30643 BH-30236 • Novel, non-covalent, brain- • Potent macrocyclic CLK inhibitor active, macrocyclic OMNI-EGFR • Modulating splicing, DNA inhibitor damage repair and • Super-potency across broad apoptosis
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