Corporate Presentation

Transcription

1 Corporate Presentation September 2018 Kadmon Holdings, Inc. 1

2 Disclaimers This presentation contains forward looking statements that are based on the beliefs and assumptions and on information currently available to management of Kadmon Holdings, Inc. (the Company ). All statements other than statements of historical fact contained in this presentation are forward-looking statements. Forward looking statements include information concerning the initiation, timing, progress and results of clinical trials of the Company s product candidates, the timing or likelihood of regulatory filings and approvals for any of its product candidates, and estimates regarding the Company s expenses, future revenues and future capital requirements. In some cases, you can identify forward-looking statements by terminology such as may, will, should, expects, plans, anticipates, believes, estimates, predicts, potential or continue or the negative of these terms or other comparable terminology. There are important factors that could cause the Company s actual results to differ materially from those expressed or implied by the forward-looking statements, including those factors discussed under the caption entitled Risk Factors in the Company s filings with the U.S. Securities and Exchange Commission ( SEC ), including the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2017 and Quarterly Report on Form 10-Q for the quarter ended June 30, 2018, filed pursuant to Section 13 of the Securities Exchange Act of 1934, as amended, with the SEC. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the Company s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent the Company s beliefs and assumptions only as of the date of this presentation. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, the Company assumes no obligation to publicly update any forward looking statements for any reason after the date of this presentation to conform any of the forward-looking statements to actual results or to changes in its expectations. 2

3 Kadmon: Developing Innovative Therapies for Unmet Needs Therapeutic Focus: Inflammation, Fibrosis and Immuno-oncology Late-stage, New-York based biotech company (NYSE: KDMN) ROCK inhibitor platform in inflammatory and fibrotic diseases Lead clinical candidate: KD025, a ROCK2 inhibitor cgvhd: Registration trial initiating September 2018 Portfolio of ROCK inhibitors for fibrotic diseases Lead candidate KD045 entering the clinic 2H 2019 Biologics platform developing IL-15-containing fusion proteins for immuno-oncology (I-O) Genetic disease product platform in Wilson s disease and PKD Commercial operation Supports development and future commercialization of clinical-stage product candidates 3

4 ROCK Inhibitor Platform 4

5 Kadmon Therapeutic Focus: ROCK Inhibition ROCK Signaling Pathway Plays a Key Role in Multiple Tissue Types Rho-associated coiled-coil kinase (ROCK) is a serine/threonine kinase Mediates a wide range of functions, including cell movement, shape, differentiation and function 1 Two isoforms exist: ROCK1 and ROCK2 1 ROCK is ubiquitously expressed, with high levels in smooth muscle tissues, brain and heart 2 Kadmon research has helped define the role of ROCK signaling in autoimmune, inflammatory and fibrotic disease ROCK2 signaling modulates inflammatory response Pan-ROCK signaling regulates multiple fibrotic processes ROCK inhibition has demonstrated therapeutic potential in a wide range of diseases 1 Small GTPases. 2014; 5: e Post-Genomic Cardiology (Second Edition). 2014, Pages

6 ROCK2 Plays Key Role in Autoimmune and Inflammatory Disease ROCK2 Rebalances Immune Response to Treat Immune Dysfunction ROCK2 inhibition down-regulates pro-inflammatory Th17 responses and increases Treg function, helping to resolve immune dysregulation Reduces STAT3 phosphorylation and increases STAT5 phosphorylation ROCK2 inhibition re-establishes immune homeostasis ROCK2 Activation ROCK2 Inhibition STAT3 (Th17) Inflammation RORgt IRF4 STAT5 (Treg) STAT3 (Th17) STAT5 (Treg) Resolution Inflammation Resolution 6

7 ROCK is Central Regulator in Pathways of Fibrotic Diseases ROCK Regulates Multiple Pro-Fibrotic Processes, Including Myofibroblast Activation ROCK is downstream of major pro-fibrotic mediators, including: Transforming growth factor beta (TGF-β) Connective tissue growth factor (CTGF) Lysophosphatidic acid (LPA) ROCK regulates fibroblast differentiation to myofibroblasts, a defining feature of pathologic fibrosis ROCK mediates stress fiber formation ROCK regulates transcription of pro-fibrotic genes, including CTGF and alpha-smooth muscle actin (α-sma) CTGF ROCK ROCK MKL1 Myofibroblast Cell MKL1 Stress fiber formation MKL1 Pro-fibrotic genes CTGF Am J Pathol Apr;185(4):

8 KD025: ROCK2-Selective Inhibitor KD025 is Kadmon s ROCK2 Inhibitor In Phase 2 Clinical Development Demonstrated a favorable tolerability profile and clinical activity in 8 completed clinical trials To date, more than 350 subjects have been dosed with KD025 for inflammatory or fibrotic diseases or as healthy volunteers Half-life: 6-8 hours Linear PK within therapeutic exposure range Demonstrated clinical activity as low as 200 mg QD Achieving median C max ~2,100 ng/ml (~5 mm) and AUC 0-24 ~10,000 h.ng/ml Little to no accumulation: Steady-state levels comparable to single dose levels in QD regimen Exposure is comparable in healthy volunteers and in inflammatory and fibrotic disease patients 8

9 Key Near-term Clinical Asset: KD025 in cgvhd Sizable Orphan Population Chronic graft-versus-host disease (cgvhd): Major complication following allogeneic hematopoietic stem cell transplant (HSCT) Occurs in ~50% of all patients who receive HSCT (~5,000 patients/year in the United States) 1,2 MoA KD025: Selective, orally available inhibitor of ROCK2 Positive Phase 2 Data in cgvhd Demonstrated effect in inflammatory and fibrotic components of cgvhd KD025 has been well tolerated Clear Path to Regulatory Approval Registration trial of KD025 in previously treated cgvhd initiating September 2018 Trial design based on FDA guidance in Type C meeting in March 2018 Orphan drug designation received October FDA. 2017, August 2 [press release]. 2 ASH. 2016, December 6 [press release]. 9

10 KD025 May Address Unmet Needs in cgvhd Current Approved Therapies in cgvhd Corticosteroids: First-line treatment for cgvhd Ibrutinib (BTK inhibitor): FDA approved for adults with cgvhd after failure of one or more lines of systemic therapy KD025 May Address Key Unmet Needs in cgvhd Need for therapy addressing inflammatory and fibrotic manifestations of CGVHD: Corticosteroids: Primarily address inflammatory components of disease Ibrutinib: Enrollment limited to patients with >25% BSA erythematous rash or NIH mouth score >4 1 KD025: Clinical responses in patients with inflammatory and fibrotic disease manifestations Need for well-tolerated cgvhd therapy: Corticosteroids: Associated with immunosuppression Ibrutinib: 24% of cgvhd patients discontinued due to adverse reactions 2 KD025: Well tolerated in clinical trials, with no drug-related SAEs; potential for long-term use 1 Blood Nov 23;130(21): Imbruvica (ibrutinib) [package insert]. Pharmacyclics LLC and Janssen Biotech,

11 Ongoing Phase 2 Trial of KD025 in cgvhd (KD ) Study of KD025 in Adults with Steroid-dependent or Steroid-refractory cgvhd Open-label, 24-week study Primary endpoint: ORR, as measured by 2014 NIH response criteria Three cohorts enrolled sequentially, following safety assessment of previous cohort: Cohort 1: KD mg QD (n=17) Cohort 2: KD mg BID (n=16) Cohort 3: KD mg QD (n=21) Enrolled complex patient population with multiple organs affected: Patients had received a median of 3 prior lines of systemic therapy 58% of patients have 4 organs involved Includes patients with both inflammatory and fibrotic disease manifestations Data as of 5/2/

12 KD025 in cgvhd: Robust Clinical Responses ORRs of 65% (11/17) and 69% (11/16) in Cohorts 1 and 2, respectively CRs observed in organs with fibrosis Highlights potential of KD025 in real-world cgvhd patients Durable responses Cohort 1: 47% (8/17) sustained responses for 20 weeks Cohort 2: 38% (6/16) sustained responses for 20 weeks 66% (22/33) of all patients reduced doses of corticosteroids 15% (5/33) of patients have completely discontinued steroids Lee Symptom Scale score improvement 1 in 55% (18/33) of patients 1 Quality of life measurement; 7-point reduction Responses Observed across all Affected Organ Systems Organ Involved n (%) Cohort 1 and 2 Responders (n=22) CR n (%) PR n (%) ORR n (%) Upper GI 6 (27) 6 (100) 0 (0) 6 (100) Lower GI 3 (14) 3 (100) 0 (0) 3 (100) Esophagus 1 (5) 1 (100) 0 (0) 1 (100) Liver 1 (5) 1 (100) 0 (0) 1 (100) Mouth 15 (68) 7 (47) 4 (27) 11 (73) Joints and fascia 16 (73) 1 (6) 9 (56) 10 (63) Eyes 17 (77) 3 (18) 7 (41) 10 (59) Skin 16 (73) 5 (31) 4 (25) 9 (56) Lungs 7 (32) 0 (0) 1 (14) 1 (14) 12

13 KD025: Well Tolerated in Patients with cgvhd in Ph2 Trial No drug-related SAEs KD025 Safety Allows patients to continue on treatment and maintain responses Allows for long-term KD025 use No apparent increased risk of opportunistic infection Infections are a common consequence of immunosuppressants frequently used to treat cgvhd Safety Overview, n (%) Cohort 1 (N=17) Cohort 2 (N=16) Median weeks of treatment Any adverse event 16 (94) 15 (94) Grade 3+ event 9 (53) 9 (56) SAE 5 (29) 5 (31) Grade 5 AE 0 0 Drug-related events (per investigator) Any related AE 6 (35) 10 (63) Related AE leading to discontinuation 1 2 (12) 0 Related Grade 3+ event 2 (12) 5 (31) Related SAE Headache, diarrhea AEs were overall consistent with those expected in cgvhd patients receiving corticosteroids 13

14 KD : Open-Label Registration Trial Based on FDA guidance in Type C meeting, Kadmon will initiate a registration trial of KD025 in cgvhd in September 2018 Open-label, two-arm trial of two KD025 doses (200 mg QD and 200 mg BID) Either dose may be considered for registration Adults with 2 prior lines of systemic therapy for cgvhd R KD mg QD (n=63) KD mg BID (n=63) Treat to progression Primary Endpoint: ORR Key Secondary Endpoint: Duration of response 14

15 Phase 2 Clinical Trial of KD025 in Scleroderma Initiating 1H 2019 Strong Scientific Rationale for KD025 in Scleroderma (Systemic Sclerosis) Chronic multi-system disease characterized by skin thickening and internal organ fibrosis Major unmet need: Affects 75, ,000 people in the United States 1 No FDA-approved targeted therapies KD025 demonstrated effect in sclerodermatous cgvhd models Phase 2 clinical study of KD025 in scleroderma (KD ) initiating 1H 2019 KD025 Reversed Clinical Signs of Sclerodermatous cgvhd (Preclinical Mouse Model) 2 Skin GVHD Score Skin Vehicle (Day 51) KD025 (Day 51) 1 American College of Rheumatology, Blood 2016: 127: Vehicle KD025 15

16 ROCK activity (fold) ROCK activity (fold) ROCK Signaling Affects Key Fibrotic Processes Research by Kadmon and Others has Demonstrated the Role of ROCK in Fibrosis ROCK Activity is Enhanced in Regions of Fibrosis Recent studies have identified novel roles for ROCK in fibrotic pathogenic processes, including: TGFβ activation and CTGF expression Endothelial barrier integrity Human ** Mouse ** Collagen deposition and fibroblast differentiation Kadmon research has determined that both ROCK isoforms play a key role in cytoskeletal organization, a key component of fibrosis 2 0 Non-IPF Ctrl IPF ROCK activity measured in human IPF samples and mouse fibrotic lungs (ELISA-based assay) 2 0 Sal Bleo Adapted from Zhou Y et al., JCI,

17 KD025: Demonstrated Proof of Concept in IPF KD025: Demonstrated Clinical Activity and Tolerability in Ongoing Phase 2 Clinical Trial KD : Open-label, 24-week trial of 39 patients randomized 2:1 to receive KD mg QD or Best Supportive Care (BSC) KD025 slowed the decline in lung function in IPF patients at 24 weeks: Absolute change in FVC of -50 ml in KD025 patients (n=24), compared to -175 ml with BSC (n=11) KD025 was well tolerated, with no drug-related SAEs Trial expanded to include an additional 40 patients, increasing total enrollment to ~81 patients Data to support the development of Kadmon s novel ROCK inhibitors for fibrotic diseases Data as of 3/13/

18 KD045: Lead ROCK Inhibitor Candidate for Fibrosis Kadmon ROCK Inhibitor Platform Kadmon research has validated the role of ROCK signaling in fibrosis KD045 Kadmon has identified and developed proprietary next-generation pan-rock inhibitors for fibrotic diseases G-loop Developing candidates with enhanced potency and AGC-kinase selectivity hinge KD045: Lead candidate selected for clinical development Activation loop Demonstrated activity in multiple in vivo pharmacology models, including in models of bleomycin-induced lung fibrosis and renal fibrosis Selectively targets ROCK, exhibiting favorable safety profile Entering the clinic in 2H 2019 for fibrotic disease indications, including IPF 18

19 Other Kadmon Platforms 19

20 % survival Tumor size (mm 2 ) Biologics Platform Developing IL-15 Fusion Proteins for I-O Lead Candidate: KD033 (anti-pd-l1/il-15 Fusion Protein): Entering Clinic 2H 2019 Demonstrated efficacy in multiple syngeneic mouse models Significantly inhibited tumor growth in PD-L1-expressing murine models resistant to approved I-O therapies Induced immune system memory KD033 surrogate-treated MC38 colon adenocarcinoma mouse model survived tumor rechallenges 2000 Tumor Growth Inhibition Post Rechallenge 100 Vehicle D7A8 10 mg/kg IP QWx4 KD033 surrogate 3.3 mg/kg IP QWx Non-responding tumors Responding tumors 50 n = 12 *** Days after re-challenge *** 0 Dosing, once a week Re-challenge Day Days after inoculation Re-challenge Day

21 Genetic Diseases Platform: PKD and WD Tesevatinib for Polycystic Kidney Disease Polycystic kidney disease (PKD): Genetic disorder driven by EGFR and Src 600,000 in the United States are living with PKD 1 Tesevatinib: Optimal candidate for PKD Oral, reversible, potent inhibitor of EGFR and Src Well tolerated, with no drug-related SAEs in Phase 1b/2a trial Tesevatinib in ADPKD: ADPKD: Ongoing double-blind, placebocontrolled Phase 2 trial ARPKD: Ongoing Phase 1 safety study of tesevatinib liquid formulation 1 National Kidney Foundation, National Organization for Rare Disorders, For up to 30 days KD034 for Wilson s Disease Wilson s Disease (WD): Genetic disorder characterized by excess copper accumulation 9,000 in the United States are affected by WD 1 KD034: generic formulation of trientine hydrochloride for WD Two ANDAs submitted to the FDA for KD034 (bottle and blister pack) Blister pack offers room temperature stability 2 Kadmon is in dialogue with the FDA regarding regulatory approval for KD034 21

22 Commercial Operation 22

23 Kadmon Pharmaceuticals: Specialty-Focused Commercial Operation Specialty-Focused Commercial Operation Kadmon Pharmaceuticals is a wholly-owned subsidiary focused on specialty pharmaceuticals Experience in specialty pharmacy distribution channel Currently markets and distributes products for a variety of indications Supports development and future commercialization of Kadmon s clinical product candidates Capabilities include CMC, regulatory, quality assurance, compliance and pharmacovigilance Kadmon commercial infrastructure based in Warrendale, PA Kadmon will leverage its commercial organization to market its products, if approved 23

24 Summary 24

25 Kadmon Summary ROCK Inhibitor Platform Biologics Program Genetic Disease Product Candidates Commercial Operation MeiraGTx Ownership KD025: ROCK2 inhibitor in clinical development Chronic graft-versus-host disease (cgvhd): Registration trial initiating September 2018 Scleroderma (systemic sclerosis): Phase 2 planned 1H 2019 Developing portfolio of ROCK inhibitors for fibrotic diseases Lead candidate KD045 entering the clinic 2H 2019 Developing unique product candidates for immuno-oncology Lead candidate KD033 entering the clinic 2H 2019 Tesevatinib: EGFR inhibitor in ongoing Phase 1/2 clinical trials for polycystic kidney disease KD034: Genetic trientine hydrochloride formulation for Wilson s disease Two ANDAs currently under FDA review Supports development and future commercialization of clinical-stage product candidates Kadmon transferred its gene therapy platform to a subsidiary of MeiraGTx Holdings plc ( MeiraGTx ) and owns 13% of MeiraGTx 1 1 As of June 30,

26 Financial Profile KDMN Financial Summary Cash and cash equivalents of $131.5 million as of June 30, ,101,776 common shares outstanding as of August 4, 2018 Trades on the NYSE under the ticker symbol KDMN 26