Kyntra Bio, Inc. · NASDAQ:KYNB
Kyntra Bio — Fibrogen — Investor Day (June 2024)
45 slides from Kyntra Bio's investor day presentation, Jun 26, 2024
Slide 1: Virtual KOL Investor Event Series Part II: FG-3246 in mCRPC
Virtual KOL Investor Event Series Part II: Review FG-3246 Development Program in Metastatic Castration-Resistant Prostate Cancer Hosted by FibroGen Inc. Wednesday, June 26, 2024
Slide 2: Forward-Looking Statements
This presentation contains “forward-looking” statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, business strategy, and plans, and objectiv
Slide 3: FibroGen Strategic Pillars and Investment Highlights
FibroGen Strategic Pillars and Investment Highlights Pamrevlumab readouts for pancreatic cancer, targeting a significant unmet medical need and representing a multi-billion-dollar revenue opportunity: ADC=antibody drug conjugate; CIA=chemotherapy-induced anemia; IND=investigational new drug; mAb=mon
Slide 4: Review FG-3246 Development Program in mCRPC
Rahul Aggarwal, MD Associate Director for Clinical Sciences, UCSF Helen Diller Family Comprehensive Cancer Center Professor of Medicine UCSF Division of Hematology/Oncology FG-3246 is an investigational drug and not approved for marketing by any regulatory authority. Review FG-3246 Development Progr
Slide 5: Prostate Cancer Deep Dive
Dr. Rahul Aggarwal Prostate Cancer Deep Dive Rahul Aggarwal, MD
Slide 6: Prostate Cancer Facts
Prostate Cancer Facts 3.4 million men live with prostate cancer in the US It is the second most common cancer type after breast cancer. ~13% of men will be diagnosed with prostate cancer at some point during their lifetime While most men diagnosed with prostate cancer can still live long lives, ther
Slide 7: Prostate Cancer Diagnosis and Progression Overview
Prostate Cancer Diagnosis and Progression Overview Source: DRG, 2024 Newly Diagnosed Low & Intermediate Risk (Hormone Sensitive) Newly Diagnosed High Risk & N1M0 (Hormone Sensitive) Newly Diagnosed Metastatic (Hormone Sensitive) Biochemical Recurrent Cases Biochemically Recurrent (Hormone Sensitive)
Slide 8: Prostate Cancer Diagnosis and Progression Overview
Prostate Cancer Diagnosis and Progression Overview Source: DRG, 2024 Newly Diagnosed Low & Intermediate Risk (Hormone Sensitive) Newly Diagnosed High Risk & N1M0 (Hormone Sensitive) Newly Diagnosed Metastatic (Hormone Sensitive) Biochemical Recurrent Cases Biochemically Recurrent (Hormone Sensitive)
Slide 9: mCRPC Treatment Landscape
Dr. Rahul Aggarwal mCRPC Treatment Landscape
Slide 10: Timeline of FDA Approvals in Metastatic CRPC
Timeline of FDA Approvals in Metastatic CRPC
Slide 11: mCRPC Treatment Algorithm based on NCCN Guidelines
mCRPC Treatment Algorithm based on NCCN Guidelines Version 3.2024 Color Key Abbreviations: AR-Tx = AR-targeted therapy AA = abiraterone ENZA = enzalutamide APA = apalutamide DARO = darolutamide D = docetaxel CABAZ = cabazitaxel AVPC = aggressive variant PCa NEPC = neuroendocrine PCa Lu-PSMA = 177Lu-
Slide 12: Evolving Treatment Landscape in Post-AR, Chemo-Naïve mCRPC
Evolving Treatment Landscape in Post-AR, Chemo-Naïve mCRPC Non-Targeted Efficacy Benchmarks (US, 2024): ARSI Switch rPFS: 5.5m-6.5m, Chemo rPFS: 8.0m-8.5m Targeted Efficacy Benchmarks (US, 2024): Post ARSI/ Pre Chemo rPFS: 9.5m-12m Rucaparib* vs. AA/ENZA or D (TRITON3) in BRCA mut Months 177Lu-PSMA-
Slide 13: Intermediate Endpoints in Metastatic CRPC
Intermediate Endpoints in Metastatic CRPC Radiographic Progression-Free Survival PSA50 and PSA90 response rates Objective response rate The only surrogate endpoint that has been accepted for regulatory approval BICR and use of standard criteria (PCWG3 + modified RECIST 1.1) Useful for gauging prelim
Slide 14: Recently Reported Results for Investigational Treatments in mCRPC
Recently reported results for Investigational treatments in development for mCRPC Drug Name/Company Target/MOA Population PSA50 ORR (%) rPFS (median) or duration of tx Safety ARX517 Ambrx (now JNJ) ADC (amberstatin) targeting PSMA Metastatic CRPC, no biomarker selection, ≥ 2 prior systemic tx 52% (d
Slide 15: FG-3246 Product Characteristics and Mechanism of Action
Dr. Rahul Aggarwal FG-3246 Product Characteristics and Mechanism of Action FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.
Slide 16: FG-3246 Novel Antibody-Drug Conjugate
FG-3246 Therapeutic Novel antibody-drug conjugate (ADC) Targeting antibody: YS5FL is a fully-human IgG1 monoclonal antibody to tumor-selective epitope of CD46 Payload: MMAE - Potent anti-microtubule agent CD46 Transmembrane protein negatively regulates the complement system Upregulated during tumori
Slide 17: FG-3246 Clinical Data Overview
Dr. Rahul Aggarwal FG-3246 Clinical Data Overview FG-3246 is an investigational drug and not approved for marketing by any regulatory authority.
Slide 18: FOR46-001 Phase I Monotherapy Study
Dr. Rahul Aggarwal FOR46-001 Phase I monotherapy study of FG-3246 administered Q3W in patients with metastatic castration resistant prostate cancer (mCRPC) Study sponsored and conducted by FORTIS NCT03575819 FG-3246 is an investigational drug and not approved for marketing by any regulatory authorit
Slide 19: Study Overview
Study Overview Phase 1 Study Design Primary Endpoints: Evaluate the safety and tolerability of FG-3246 in mCRPC patients, Determine the MTD and/or recommended Phase 2 dose in mCRPC patients Secondary Endpoints: Characterize the PK of FG-3246, YS5FL, and MMAE, Efficacy including rPFS, PSA50, and obje
Slide 20: Study Overview: Eligibility Criteria
Study Overview Eligibility Criteria Progressive metastatic castration resistant prostate cancer (CRPC) by PCWG3 criteria Prior treatment with at least one androgen signaling inhibitor (e.g., abiraterone, enzalutamide) No prior taxane for the treatment of metastatic CRPC Prior taxane for castration-s
Slide 21: FOR46-001 Baseline Characteristics
FG-3246 - FOR46-001 Baseline Characteristics Median age, years (range) 69 (42 – 81) Race, n White/Black/Asian/Native American 43 / 5 / 2 / 1 Median PSA, ng/mL (range) 41 (0.2 – 1627) Measurable disease (RECIST 1.1), n (%) 31 (60.8) Type of disease progression at study entry, n (%) PSA Node only (no
Slide 22: FG-3246 Phase 1 Safety Summary
Safe and generally well tolerated Adverse events consistent with other MMAE based antibody-drug conjugate (ADC) therapies Peripheral Neuropathy All Grades – 34.1%, Grade 3 or higher – 2.3% Neutropenia All Grades – 45.5%, Grade 3 or higher – 36.4% Infusion-Related Reactions All Grades - 47.7%, Grade
Slide 23: Adverse Events by Patient
All Grades by Patient (≥ 10%) All Grades N (%) ≥ Grade 3 N (%) Fatigue 25 (56.8) 3 (6.8) Weight decreased 23 (52.3) 1 (2.3) Infusion related reaction 21 (47.7) 1 (2.3) Nausea 20 (45.5) 0 Neutropenia 20 (45.5) 16 (36.4) Constipation 19 (43.2) 0 Decreased appetite 16 (36.4) 1 (2.3) Diarrhoea 16 (36.4)
Slide 24: 8.7 Month rPFS - Potentially Clinically Meaningful Efficacy
8.7 Month rPFS - Potentially Clinically Meaningful Efficacy Phase 1 monotherapy Median rPFS (months) Selected Cohorts (N=40): 8.7 months (n=27: 26 PD; & 1 Death Event) Selected Cohorts: Dose escalation cohorts-level > 1.2 mg/kg, combined with cohort 1 (adenocarcinoma) of the Expansion cohort
Slide 25: Meaningful PSA50 Response Observed in Selected Cohorts
Meaningful PSA50 Response Observed in Selected Cohorts, Represents Compelling Indication of Clinical Activity Phase 1 monotherapy PSA Decline Selected Cohorts (N=39): PSA Decline by >50%: 14 (35.9%) PSA Decline by >50% confirmed at least 2 weeks later: 12 (30.8%)x Selected Cohorts: Dose escalation c
Slide 26: Confirmed Objective Response Rate
Selected Cohorts (N=25) Confirmed ORR 5 (20%) Complete Response 0 Partial Response 5 (20%) Stable Disease 15 (60%) Prog. Dis 4 (16%) Indeterminate 1 (4%) Confirmed Objective Response Rate RECIST Evaluable Set (Selected Cohorts) Selected Cohorts: Dose escalation cohorts-level > 1.2 mg/kg, combined wi
Slide 27: Duration of Response in Selected Cohorts
Duration of Response (DOR) in Selected Cohorts Median Tumor DOR (months) Selected Cohorts (N=25): 7.5 (N=5; 5 with ORR) Selected Cohorts: Dose escalation cohorts-level > 1.2 mg/kg, combined with cohort 1 (adenocarcinoma) of the Expansion cohort Phase 1 monotherapy
Slide 28: FG-3246 Phase 1 Monotherapy Summary
Single agent activity in heavily pretreated mCRPC (median 5 prior lines of therapy) 8.7 months rPFS Objective Response Rate (ORR) 20% Duration Of Response (DoR) 7.5 months PSA50 = 36% Safe and well tolerated to date Doses selected for Phase 2/3 registrational trial: 1.8 and 2.4 mg/kg 2.4 mg/kg and/o
Slide 29: FG-3246 + Enza Phase 1b ASCO 2024 Interim Data
Dr. Rahul Aggarwal Investigator Sponsored Study by Dr Rahul Aggarwal FG-3246 + Enza Phase 1b ASCO 2024 Interim Data Phase 1b Dose Escalation Study of FG-3246, a Novel Antibody-Drug Conjugate Targeting a Tumor Specific Epitope of CD46, in Combination with Enzalutamide (Enza) in Patients with mCRPC NC
Slide 30: ARSIs Up-regulate CD46 in mCRPC and Sensitize to FG-3246
ARSIs Up-regulate CD46 in mCRPC and Sensitizes to FG-3246 Tx Provides rationale for combination therapy Su et al., JCI Insight 2018 LNCaP-C4-2B Du145 CD46 ADC Ctr ADC Ctr ADC + ASI ASI + CD46 ADC shows enhanced killing (EC50 on LNCaP-C4-2B: 13 pM vs. 226 pM)
Slide 31: Phase 1b Endpoints and Study Design
Phase 1b Primary Endpoint Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of FG-3246 in combination w/ enzalutamide Secondary Endpoints PSA50 Response Rate Objective Response Rate by RECIST 1.1 criteria Median radiographic progression-free survival (rPFS) Overall Survival Frequency
Slide 32: Study Design: Trial Schematic
Study Design: Trial Schematic Phase 1b/2 study evaluating FOR46 in combination with enzalutamide in patients with mCRPC after prior progression on abiraterone. Dose Escalation with Expansion (3+3) dependent on DLTs. Phase 1b/2 Treatment Cycle: FOR46 21 Days per cycle & 160mg/d QD Enzalutamide Phase
Slide 33: Treatment-related Adverse Events
Treatment-related Adverse Events Treatment-related AEs that lead to treatment discontinuation included increased LFTs (transaminases) (n=1), Neuropathy, Grade 2 (n=3), and Hyponatremia (n =1) Phase 1b combination Presented at ASCO June 2024
Slide 34: Clinical Outcomes: DoT, rPFS
Clinical Outcomes: DoT, rPFS Median time on treatment for patients in all dose levels (N = 17) was 6 months (range: 1 – 18) with 3 patients still on treatment. The preliminary estimate of median radiographic progression-free survival was 10.2 months. Phase 1b combination Duration of Treatment Radiog
Slide 35: Clinical Outcomes: PSA
Clinical Outcomes: PSA The majority of patients (12/17 evaluable, 71%) experienced a decline in PSA levels post-treatment 5 of the 12 patients (42%) that experienced PSA decline had previous progression on enzalutamide There were two patients who experienced ≥ 50% decline from baseline in PSA Phase
Slide 36: Zr-89 labeled YS5 Demonstrates Tumor Specific Uptake
Zr-89 labeled YS5 Demonstrates Tumor Specific Uptake Phase 1b combination Axial PET/CT fusion images obtained 5 days following administration of 89Zr-DFO-YS5 in a 72 year old man with history of prostate adenocarcinoma, with prior treatments of Lupron, abiraterone, and enzalutamide, and a PSA of 53.
Slide 37: Phase 1b Conclusions: FG-3246 + Enzalutamide
The MTD and recommended phase 2 dose of FOR46 was established as 2.1 mg/kg adjusted body weight with primary G-CSF prophylaxis in combination with enzalutamide 160 mg daily Preliminary anti-tumor activity was observed with PSA declines in 12/17 (71%) of evaluable pts, and a preliminary estimate of m
Slide 38: Opportunity in mCRPC and Lifecycle Management
Opportunity mCRPC and Lifecycle Management Deyaa Adib, MD FibroGen Chief Medical Officer
Slide 39: FG-3246 Presents a Unique Opportunity in mCRPC
FG-3246 Presents a Unique Opportunity in mCRPC Novel Mechanism of Action and potential First-in-Class Opportunity ADC – antibody against novel target tethered to a validated chemotherapy payload Binds a unique epitope on CD46 present on cancer cells, including prostate/colorectal, but absent in most
Slide 40: Development of a CD46 Biomarker is Integral to Development Strategy
Development of a CD46 Biomarker is an Integral Part of the Development Strategy Likely that patient selection biomarker is required to achieve clinically differentiated profile in prostate cancer, based on early clinical data and highly competitive mCRPC market Estimate that 50%-70% of mCRPC patien
Slide 41: Planning for Seamless Phase 2/3 RCT in Pre-Chemo mCRPC
Planning for Seamless Phase 2/3 RCT > 2L Pre-Chemo mCRPC Randomized, dose optimization, biomarker-driven, adaptive phase 2/3 design: FG-3246 vs. ARSI switch* Ph3 in CD46high patients: FG-3246 vs. ARSI switch* Open label-adaptive design Primary EP: rPFS Secondary EP: OS Biomarker strategy: PET46 vs.
Slide 42: Treatment Option Landscape and Target Product Profile
Treatment Option Landscape for Pre-chemo mCRPC and Target FG3246 Product Profile FG-3246 Target Product Profile ARSI switch Chemo PSMA targeted radioligands Patient population CD46-high selected Unselected Unselected PSMA-high selected rPFS (months) >10m 5.6m-6.4m 8.3m 9.5 - 12.0m OS (months) 28.6m
Slide 43: FG-3246 & PET46 Biomarker - Vision and Strategy
Pursue accelerated registrational path to pre-chemo mCRPC Establish FG-3246 in pre-chemo mCRPC in CD46high patients (monotherapy & combination therapy) Establish PET46 biomarker as standard of care diagnostic Expand footprint in prostate cancer by moving into earlier stages of disease Launch in othe
Slide 44: Q&A Session
Q&A Session
Slide 45: Thank You
Thank You