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| Item 7.01. | Regulation FD Disclosure. |
On August 14, 2023, Delcath Systems, Inc. (the “Company”) issued a press release announcing that the U.S. Food and Drug Administration (“FDA”) approved the Company’s HEPZATO Kit™ (“HEPZATO”) for the treatment of adult patients with unresectable hepatic-dominant metastatic uveal melanoma. The press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
On August 14, 2023, the Company released an updated corporate presentation on the “Events & Presentations” section of the Company’s website at https://delcath.com/investors/events-presentations/. The Company has scheduled a conference call to take place on August 15, 2023, relating to the FDA approval of HEPZATO. A copy of the corporate presentation is furnished as Exhibit 99.2 to this Current Report on Form 8-K.
The information in this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (“Exchange Act”), or otherwise subject to the liabilities of that Section, and shall not be deemed incorporated by reference in any registration statement or other filing pursuant to the Securities Act of 1933, as amended, or the Exchange Act, except as otherwise expressly stated in such filing.
| Item 8.01. | Other Events. |
On August 14, 2023, the FDA approved HEPZATO for the treatment of adult patients with unresectable hepatic-dominant metastatic uveal melanoma.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Press Release, dated August 14, 2023. | |
| 99.2 | Corporate Presentation. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
| DELCATH SYSTEMS, INC. | ||||||
| Date: August 15, 2023 | By: | /s/ Gerard Michel | ||||
| Name: | Gerard Michel | |||||
| Title: | Chief Executive Officer | |||||
Exhibit 99.1
Delcath Systems, Inc. Announces FDA Approval of HEPZATO KIT™ for the Treatment of Adult Patients with Unresectable Hepatic-Dominant Metastatic Uveal Melanoma
HEPZATO KIT is the only FDA approved liver-directed therapy to treat metastatic uveal melanoma
Approval includes treatment naïve and previously treated patients and is not limited by HLA genotype
Delcath to hold Business Update Call on August 15, 2023 at 8:00 a.m. Eastern Time
NEW YORK, August 14, 2023/PRNewswire/ - Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, announced that today the US Food and Drug Administration (FDA) approved HEPZATO KIT (melphalan/Hepatic Delivery System) as a liver-directed treatment for adult patients with metastatic uveal melanoma (mUM) with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.
mUM is a rare and aggressive form of metastatic cancer with a US incidence of approximately 1,000 cases per year. Ninety percent of mUM involves the liver, and liver failure is often the cause of death. National Comprehensive Cancer Network (NCCN) guidelines recommend liver-directed therapies for mUM patients with liver metastases. HEPZATO KIT is the only liver-directed therapy approved by the FDA for the treatment of mUM and percutaneous hepatic perfusion (PHP), the procedure enabled by HEPZATO KIT, is already included in the NCCN guidelines.
“FDA approval of HEPZATO KIT marks the beginning of a new chapter for Delcath and the culmination of the Company’s commitment to bring this treatment option to patients suffering from metastatic uveal melanoma,” said Gerard Michel, Delcath’s Chief Executive Officer. “We look forward to partnering with cancer centers across the country to build a network of treatment sites trained in the use of this novel therapy.”
The Company plans to have commercial product available in the fourth quarter, and patients will continue to be enrolled and treated at Expanded Access Program (EAP) sites.
The approval of HEPZATO KIT was based primarily on the results of the FOCUS Study (NCT02678572), a Phase 3, single arm, multicenter, open label study, which administered HEPZATO (melphalan) via the hepatic delivery system (HDS) during a PHP procedure. Ninety-one (91) patients received treatment every 6 to 8 weeks, for up to 6 treatments. The main efficacy endpoints were objective response rate (ORR) and
duration of response (DoR) as assessed by an independent review committee using RECIST v1.1. ORR was 36.3% (95% CI: 26.4, 47.0) and median DoR was 14 months (95% CI: 8.3, 17.7). The Disease Control Rate (DCR) observed in treated patients was 73.6% (95% CI: 63.3, 82.3) with 7 complete responses (7.7%), and 26 (28.6%) partial responses.
The patient population enrolled in the FOCUS Study included patients with hepatic and extra-hepatic lesions subject to a treatment plan, as well as both treatment naïve (56.0%) and previously treated (44.0%) patients, irrespective of HLA genotype.
The HEPZATO KIT prescribing information has a boxed warning, which includes three sections: toxicity related to the procedure, myelosuppression and a Risk Evaluation and Mitigation Strategy program, commonly known as REMS, to manage and mitigate these risks. Serious adverse events associated with the PHP procedure with the HEPZATO KIT, such as hemorrhage, hepatocellular injury, and thromboembolic events, occurred in less than 5% of treated patients. Myelosuppressive adverse events including thrombocytopenia, anemia, and neutropenia, are well-known and predictable side effects of melphalan and are routinely managed with standard supportive care measures.
The HEPZATO KIT REMS is designed to ensure consistent conduct of the PHP procedure and that only treatment teams who have received appropriate training perform the PHP procedure.
“HEPZATO KIT is the only liver-directed therapy that can treat the whole liver,” said Vojislav Vukovic, Delcath’s Chief Medical Officer. “Scientific literature supports that HEPZATO KIT may have broad applicability in other tumor types, and we intend to expand our development efforts beyond uveal melanoma given the high incidence of unresectable hepatic dominant tumors.”
The approval effectively triggers the second tranche of financing tied to the previously announced March 29, 2023 Private Investment in Public Equity (PIPE) financing. Participants in the PIPE have 21 days to exercise their Tranche A warrants, translating to up to approximately $34.9 million of additional funding to Delcath. In addition, upon the Company’s announcement of recording at least $10.0 million in quarterly U.S. revenue from the commercialization of HEPZATO KIT, participants in the PIPE will have 21 days to exercise their Tranche B warrants, resulting in up to an additional $24.9 million in funding to Delcath.
About HEPZATO KIT
HEPZATO KIT is a combination product that administers HEPZATO (melphalan), a well-known and long-approved chemotherapeutic agent, directly to the liver through Delcath’s novel device delivery system, the Hepatic Delivery System (HDS), which permits higher drug exposure in target tissues while limiting systemic toxicity. The use
of the HDS allows a healthcare provider team to surgically isolate the liver while the hepatic venous blood is filtered during melphalan infusion and subsequent washout during a Percutaneous Hepatic Perfusion (PHP) procedure. PHP, which can only be performed with Delcath’s HDS, results in loco-regional delivery of a relatively high melphalan dose.
About Hepatic-Dominant Metastatic Uveal Melanoma
Uveal melanoma is a very rare form of cancer that affects melanocytes in the eye with approximately 5% of all melanomas being uveal. The US incidence of primary uveal melanoma is approximately 2,000 cases per year. While surgical or radiation therapy of the primary tumor is generally successful, approximately half of all patients with uveal melanoma will develop metastatic disease, primarily due to this inability to treat early micro-metastases of the primary tumor. The metastases occur predominantly in the liver (~90% of patients), and less commonly in the lungs and bones.
Prior to the approval of HEPZATO KIT, there was no approved liver-directed therapy for patients with metastatic uveal melanoma. There is one systemic therapy, KIMMTRAK® (tebentafusp-tebn), approved for a subset of mUM patients with HLA-A*02:01-positive unresectable or metastatic uveal melanoma. Because most patients, regardless of HLA-A*02:01 status, eventually progress, there is a need for both first line treatment of HLA-A*02:01- negative patients and second line treatment for HLA-A*02:01-positive patients.
The treatment of liver metastases is critical since liver failure is most often the cause of death for patients with metastatic uveal melanoma. Because of this, National Comprehensive Cancer Network guidelines recommends liver-directed therapies for patients with metastases to the liver, including embolization (i.e., transarterial chemoembolization, radioembolization or immunoembolization), ablative procedures (i.e., thermal ablation, cryotherapy) as well as PHP which can only be performed with the HEPZATO KIT. It is noteworthy that PHP was already on guidelines prior to FDA approval.
Metastatic uveal melanoma tumors in the liver tend to have a miliary pattern of spread where there are numerous radiographically evident and microscopically occult metastases in the liver. Therefore, an effective treatment should ideally treat the entire liver and allow for retreatment. None of the embolization or ablation treatments fulfill these requirements nor have any of these techniques been studied in prospective multi-center trials. The PHP procedure utilizing the HEPZATO KIT saturates the entire liver, regardless of the location or imageability of the lesions and most patients are able to undergo multiple treatments.
Please see the full Prescribing Information, including BOXED WARNING for the HEPZATO KIT.
Delcath will hold a business update conference call August 15, 2023, at 8:00 AM Eastern Time to discuss the FDA approval.
Conference Call Information
To participate in this event, dial-in approximately 5 to 10 minutes before the beginning of the call.
Event Date: Tuesday, August 15, 2023
Time: 8:00 AM Eastern Time
Participant Numbers: Toll Free: 1-833-630-1960
International: 1-412-317-1841
Webcast: https://app.webinar.net/rE345LOXL6b
CONFERENCE REPLAY
| US Toll Free: |
1-877-344-7529 | |
| International Toll: |
1-412-317-0080 | |
| Replay Access Code: |
4657227 | |
| End Date: |
August 21, 2023 | |
Important Safety Information
Patients eligible for HEPZATO should NOT have any of the following medical conditions:
| • | Active intracranial metastases or brain lesions with a propensity to bleed |
| • | Liver failure, portal hypertension, or known varices at risk for bleeding |
| • | Surgery or medical treatment of the liver in the previous 4 weeks |
| • | Active cardiac conditions including unstable or severe angina or myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease |
| • | History of allergies or known hypersensitivity to melphalan or a component or material utilized within the HEPZATO KIT including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids |
Most common adverse reactions or laboratory abnormalities occurring with HEPZATO treatment are thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased alkaline phosphatase, increased aspartate aminotransferase and dyspnea.
Severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events may occur via hepatic intra-arterial administration of HEPZATO. HEPZATO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the HEPZATO KIT REMS. Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with HEPZATO. Additional cycles of HEPZATO therapy will be delayed until blood counts have improved.
Please see the full Prescribing Information, including BOXED WARNING for the HEPZATO KIT.
About Delcath Systems, Inc.
Delcath Systems, Inc. is an interventional oncology company focused on the treatment of primary and metastatic liver cancers. The Company’s proprietary products, HEPZATO KIT™ (melphalan hydrochloride for Injection/Hepatic Delivery System) and CHEMOSAT® Hepatic Delivery System for Melphalan percutaneous hepatic perfusion (PHP) are designed to administer high-dose chemotherapy to the liver while controlling systemic exposure and associated side effects during a PHP procedure.
Forward Looking Statements
The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by the Company or on its behalf. This press release contains forward-looking statements, which are subject to certain risks and uncertainties, that can cause actual results to differ materially from those described. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Factors that may cause such differences include, but are not limited to, uncertainties relating to: the Company’s commercialization plans and its ability to successfully commercialize the HEPZATO KIT; the Company’s successful management of the HEPZATO KIT supply chain, including securing adequate supply of critical components necessary to manufacture and assemble the HEPZATO KIT; successful FDA inspections of the facilities of the Company and those of its third-party suppliers/manufacturers; the Company’s successful implementation and management of the HEPZATO KIT Risk Evaluation and Mitigation Strategy; the potential benefits of the HEPZATO KIT as a treatment for patients with primary and metastatic disease in the liver; the Company’s ability to obtain reimbursement for the HEPZATO KIT; and the Company’s ability to successfully enter into any necessary purchase and sale agreements with users of the HEPZATO KIT. For additional information about these factors, and others that may impact the Company, please see the Company’s filings with the Securities and Exchange Commission, including those on Forms 10-K, 10-Q, and 8-K. However, new risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. Accordingly, you should not place undue reliance on these forward-looking statements, which speak only as of the date they are made. We undertake no obligation to publicly update or revise these forward-looking statements to reflect events or circumstances after the date they are made.
Contact:
Investor Relations Contact:
Ben Shamsian
Lytham Partners
646-829-9701
shamsian@lythampartners.com
Exhibit 99.2 Corporate Presentation (NASDAQ: DCTH) August 14, 2023 1
Forward-looking Statements The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by the Company or on its behalf. This presentation contains forward-looking statements, which are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.Factors that may cause such differences include, but are not limited to, uncertainties relating to: the Company’s ability to successfullycommercialize the HEPZATO KIT; the Company's successful management of the HEPZATO KIT supply chain, including securing adequate supply of critical components necessary to manufacture and assemble the HEPZATO KIT; successful FDA inspections of the facilities of Delcath and third-party suppliers/manufacturers; the Company's successful implementation and management of the HEPZATO KIT Risk Evaluation and Mitigation Strategy; the potential of the HEPZATO KIT as a treatment for patients with primary and metastatic disease in the liver; our ability to obtain reimbursement for commercialized product; the Company’s ability to successfully enter into any necessary purchase and sale agreements with users of the HEPZATO KIT; the timing and results of the Company’s clinical trials, our determination whether to continue a clinical trial program or to focus on other alternative indications, and the impact of the COVID-19 pandemic or other pandemics on the completion of our clinical trials; the impact of the presentations at major medical conferences and future clinical results consistent with the data presented; uncertainties relating to the timing and results of research and development projects; and uncertainties regarding the Company’s ability to obtain financial and other resources for any research, development, clinical trials and commercialization activities. These factors, and others, are discussed from time to time in our filings with the Securities and Exchange Commission. You should not place undue reliance on these forward-looking statements, which speak only as of the date they are made. We undertake no obligation to publicly update or revise these forward-looking statements to reflect events or circumstances after the date they are made. 2
Executive Summary Delcath aims to be the leader in targeted, safe and highly-effective minimally-invasive treatments for patients with cancers of the liver. UNMET NEED HEPATIC DELIVERY COMPANY & LARGE MARKET LIVER CANCER SYSTEM (HDS) CLINICAL PROGRAM OPPORTUNITY Incidence US/EU HDS + Melphalan enables FDA Approved 8/14/23 Near-term (mUM)* • >200K primary and the Percutaneous Hepatic • Metastatic Ocular • Ultra orphan pricing metastatic liver tumors Perfusion (PHP) Procedure Melanoma (mUM) dynamic 1-14 per year • Delivers high dose • Liver failure #1 cause of • >$600M TAM in US/EU chemotherapy to the death in mUM Current local/regional entire liver • Response rates >36% Longer Term (CRC, ICC, • Limits systemic exposure • 1 Year OS** = 80% treatments Pancreatic, etc.) • Minimally invasive, • Cannot treat the whole • >>$1B TAM liver repeatable and well- Real World Evidence • Investigator interest in • Targeted to visible and tolerated • >1k commercial treatments more than 10 other accessible tumors in EU indications • Limited in their ability to US: HEPZATO KIT • Multiple single center retreat (Melphalan/HDS) publications EU: CHEMOSAT (HDS) Launch Expected Q4 ‘23 * mUM – metastatic Uveal Melanoma, also known as metastatic Ocular Melanoma **Exploratory endpoint in FOCUS trial 3
Limitations of Current Liver-Directed Therapies 1 2 Trans Arterial Chemo Embolization (TACE) Y90 » Beads obstruct blood flow to tumor and elute chemo » Radioactive beads delivered into the tumor » 50-60k treatments per year in US (and growing) » 10-15k treatments per year in US (and growing) Effective, but tumors recur & retreatment Diffuse disease: cannot be treated with a Many tumors are not imageable – limited due to damaged vasculature tumor-by-tumor modality micro-metastases are common 4 Majority of Treatment
HEPZATO KIT™: Enables Percutaneous Hepatic Perfusion (PHP) Repeatable, safe & effective liver-focused disease control ISOLATION Blood Return Hepatic venous flow is isolated, Catheter enabling 12x increased dose Chemo Chemo Isolation Filtration (Balloon) Catheter SATURATION Melphalan (chemo) treats micro Liver and macro lesions simultaneously Chemo Delivery FILTRATION Catheter Veno-veno Bypass Pump Proprietary filters remove greater 33 than 85% of chemo from the body 5
Liver-Dominant Cancers High incidence with poor prognosis UIIU S n nS c cIiin d d In c e ec in n d id c c ee e e n n c o o c ef f e L L o o iif v vf L e eL ir r v iv D D ee ro o r D m m D o iin n o m a a m in n n it t n aa n C Cn t a at C n nC c c ae e a nr r n cs s c ee rs rs* (p (p(p a art rt a(p iirt a aia lla s s rt l e e s ia tte ls s ts h h se o o h tw w o sw n n h) ) o nw ) n) Up to 50,000 DELCATH OPPORTUNITY+ Many patients with liver metastases are not amenable to surgical resection largely 80% 40,000 17 due to extensive tumor burden 30,000 Liver: Common Site of Metastases 20,000 Limited Effective Systemic Treatments 10,000 » Systemic therapies - low efficacy » Immuno-oncology agents - become less effective in the presence of metastases 0 mOM ICC mBC mNET mPC mCRC HCC Limited Overall Survival – Unresectable Liver Cancer » Often the life-limiting organ 3,4 5,6 9-12 8,9 *Metastatic Ocular Melanoma (mUM) , Cholangiocarcinoma (ICC) , Liver-dominant Breast Cancer (mBC) , Metastatic Neuroendocrine Tumors (mNET) 6 9,15 13,14 17 Metastatic Pancreatic Cancer (mPC) , Metastatic Colorectal Cancer (mCRC) , Hepatocellular carcinoma (HCC) U U.S .S. . In Inc ci id de en nc ce e
mUM: Beachhead Market Opportunity High Unmet Need, Favorable Reimbursement Environment Unmet Need Low Risk Commercial Opportunity 18 » >5,000 cases of primary ocular melanoma per year in the US/EU » FDA Approved 8/14/23 4,19 ~50% metastasize to the liver » Commercial launch 4Q ’23 » US TAM ~800 patients, Europe ~1,200 patients » Commercial team led by TheraSphere (BSX) veterans 20 » Median survival up to 12 months. » Focused commercial effort: 20 US treatment centers @ 2 » 55% of patients have no approved treatment option, most patients patients/week = ~70% TAM treated with multiple lines of therapy High Barrier to Entry Favorable US Commercial Economics » Orphan indication status allows for extended exclusivity » Favorable US reimbursement environment for ultra orphan outpatient » HEPZATO is a combination drug device regulated by CDER – no MD administered drugs traditional ANDA pathway » KIMMTRAK® (tebentafusp-tebn) (approved 1Q ‘22 for ~45% of » IP around HEPZATO limits any 505(b)(2) follow-on mUM population ) priced at an average of $790K per patient, reported $41.7M in 2Q ‘23 7
Patient Journey (Pre- Metastatic) Screening frequency dependent on risk level • Higher risk patients (50%) are ~1,000 patients screened at a high frequency ~2,000 patients Initial diagnosis & treatment • Lower risk patients (50%) are • Enucleation screened at a lower frequency • Radiation • Photodynamic therapy Medical Oncologist Ophthalmology Surveillance at Academic Center Initial screening Ophthalmologist/ Optometrists Ocular oncologist Eye specialist Ophthalmologist/ Milestone: Ocular oncologist Surveillance decision made Surveillance by Ophthalmologist/ Ocular Oncologist Caregiver Patient Medical Oncologist Surveillance at Nonacademic Center Gene expression profiling may occur here ~ 3-5 YEARS 8
Patient Journey (Post Metastatic) HEPZATO TAM: ~800 patients Most patients receive both systemic and liver-directed therapies ~1000 patients Surgical resection Surgical oncologist Treatment Liver-directed therapy Interventional radiologist Decision Systemic therapy Medical oncologist 9
Liver metastases: a significant clinical problem in mUM Half of all patients with UM develop mUM patients have micrometastases with or 21,22 systemic metastases without the presence of radiologically visible 23 metastases • The liver is involved in 90% of cases of 21,22 metastatic disease • In 50% of mUM patients, the liver is the 21,22 only site of metastasis • Most patients with mUM die from liver 22 Liver directed treatment, such as Isolated failure Hepatic Infusion* (IHP), achieves better • 1-year OS rate of patients with metastatic disease in the liver is 13%; mOS with efficacy (ORR, PFS, PFS) compared to median survival ranging from 4 to 15 26 systemic therapy 24,25 months IHP is an invasive surgical technique for delivering high doses of chemotherapy to the liver; procedure related mortality and morbidity prevented common usage. PHP is a minimally invasive, safer procedure which accomplishes the same goals as IHP and can be performed up to 6 times. 10
Diffuse/Miliary Metastatic Pattern in mUM Diffuse disease is difficult to treat with current options Solitary liver lesions are often treated with surgery or ablation Radiographically metastatic Uveal Melanoma can initially present only as focal lesions As is often the case, the true nature of the disease may only be seen upon visual confirmation Traditional liver directed therapy mechanism of action is not ideal if a whole liver treatment is needed Whole organ therapy delivers medication to a specific organ or tissue through its blood supply, then filters out the medication to minimize Actual patient sent for a liver resection based systemic exposure upon radiographic diagnosis* * Data on File 11
Estimated 80%+ of mUM Patients Are Eligible Treatment naïve and No HLA genotype Indicated Patient Population includes previously treated patients restrictions 12
Box Warnings Managed By REMS European experience has shown that the procedure can Risk Evaluation and Mitigation Strategy Program be safely conducted by Interventional Radiology team = Training & Monitoring after appropriate training REMS program goals are to standardize training, ensure consistent treatment methodology and monitor outcomes Myelosuppression is a black box warning for generic melphalan, the management of which is standard practice for oncologists 13
FOCUS Trial • Multinational, multicenter, single-arm trial Registration Clinical Trial for Patients with mUM • Efficacy Endpoints: » Primary: Objective Response Rate (ORR) compared to meta- analysis of IO therapy » Secondary: Duration of Response (DOR), Disease Control Rate (DCR), Overall Survival (OS), Progression Free Survival (PFS) • 102 patients enrolled, 91 completed treatments at 23 centers in the US and EU • HEPZATO Tx every 6-8 weeks up to a maximum of 6 14 cycles 14
FOCUS Trial • 91 treated patients Single Arm Trial Efficacy Data in PI • Trial powered to show an ORR advantage over a meta-analysis of Best Alternative Care (checkpoint Efficacy Endpoint N (%) inhibitors, chemotherapy, other liver directed therapy) ORR, n (%) 33 (36.3) • Lower bound of FOCUS ORR (26.4) is significantly [95% CI] [26.44, 47.01] higher than the upper bound of the meta-analysis (8.3%) Median DOR, months 14 • Prescribing Information includes ORR, DOR and [95% CI] [8.31-17.74] response categories • Full analysis with final data cut pending publication DCR, n (%) 67 (73.6) – manuscript in process [95% CI] [63.35, 82.31] 15
HEPZATO Response Predicts Survival Kaplan Meier Curves in Treated Populations* Exploratory Analyses* CR PR SD PD/ND ( (N=7) (N=26) N=34) (N=24) Status of OS, N (%) 1 (14.3) 17 (65.4) 29 (85.3) 20 (83.3) Events 6 (85.7) 9 (34.6) 5 (14.7) 4 (16.7) Censored † Median OS (Months) NC 28.16 19.25 11.99 95% CI [26.71, NC] [23.46, 34.46] [15.90, 23.00] [8.18, 14.03] ‡ p-value <0.0001 CR=complete response, PR=partial response, SD=stable disease, PD=progressive disease, ND=not done, BOR=best overall response Note: NC = Not calculable, due to the number of events within the stratum (n=1) † Kaplan-Meier estimates. ‡ Log-Rank test. * 02-Dec-2022 data cut, patients followed through May, 2023 Analysis Supports that ORR is Clinically Meaningful 16
OS and PFS Trend Favorable Relative to Historical Results Pre-Specified Exploratory Analyses* Secondary Endpoint N (%) Median OS, months 20.53 [95% CI] [16.79, 25.26] 1 Year OS, K-M Probability Point Estimate 0.80 [95% CI] [0.70, 0.87] Median PFS, Months 9.03 [95% CI] [6.34, 11.56] * 02-Dec-2022 data cut, patients followed through May, 2023 17
Published mUM Prospective and Retrospective Studies* Clinical Median OS Median PFS Study Type Treatment N 1 year OS Study/Publication (months) (months) AL FOCUS Single-Arm Hepzato 91 20.53 80% 9.03 systemic and liver- 33 Khoja et al 2019 Meta-Analysis 912 10.2 NA 3.3 directed therapies Rantala et al systemic and liver- Meta-Analysis 2,494 12.84 NA NA 34 2019 directed therapies 35 TN Piulats et al 2021 Single-Arm ipi plus nivo 52 12.7 NA 3.0 ipi plus (pembro or 36 AL Heppt et al 2019 Single-Arm 64 16.1 NA 3.0 nivo) TN tebentafusp 252 21.7 73% 3.3 37 Nathan et al 2021 Randomized TN control 126 16 59% 2.9 Ipi = ipilimUMab, nivo = nivolumab, pembro = pemUMab TN = Treatment Naïve, AL = Any Line *Studies from 2019 or later with >50 patients 18
All Adverse Reactions Adverse Events N=95 Primarily Hematological All Grades (%) Grades 3 or 4 (%) Hypotension 13 3 Dyspnea 23 2 Abdominal Pain 39 1 Diarrhea 17 1 Musculoskeletal Pain 46 1 Hemorrhage 15 1 Most hematological side effects Nausea 57 0 result from melphalan Vomiting 35 0 Fatigue 65 0 Pyrexia 16 0 Side effect profile similar to other Groin Pain 11 0 cytotoxics commonly Used By Cough 15 0 Oncologists Headache 19 0 Lethargy 12 0 Dizziness 11 0 Contusion 17 0 Decreased appetite 16 0 19
Referring Centers HEPZATO Treating Center Patients Referred to Multidisciplinary Anesthesiologist Treatment Teams Medical Medical Oncologist Oncologist Perfusionist Interventional Radiologist Oncologists Are Generally Trained Treating Team Medical Medical the Decision Makers Oncologist Oncologist 20
Training Key to Expanding Number of Treating Sites and Capacity Multidisciplinary Teams to Be Expanded To Increase Both Training Capacity and Patient Flow Expanded Treatment Expand Treatment Teams Today Increase # Sites Increase # HCP Trainers & Treatment Capacity Capacity Moffit UT Memphis Duke 21
Plan To Launch at 10 Treating Sites Leveraging EAP and Longitudinal Data to Build Referral Networks EAP – Currently 3 Sites • Provide immediate access to patients • First Commercial Sites • Train new medical teams to use Hepzato after launch Leverage Longitudinal Data • Partnered with data provider to access patient level longitudinal data with 3-week refresh Active EAP sites • Accurately map and quantify surveillance, referral and treatment patterns at the patient and MD level Planned Initial Hepzato Treatment Sites 22
Treating Centers – Current Targets for Launch Institution City Status Moffitt Cancer Center Tampa, Florida EAP - Open and Enrolling Duke University Durham, North Carolina EAP - Open and Enrolling University of Tennessee Memphis, Tennessee EAP - Open and Enrolling Stanford University Stanford, California EAP - Plans to join Ohio State University Columbus, Ohio EAP - Plans to join Mayo Clinic Hospital Jacksonville, Florida EAP - Plans to join HonorHealth Scottsdale, Arizona Confirmed interest in being a treating center Thomas Jefferson University Philadelphia, Pennsylvania Confirmed interest in being a treating center University of Miami Miami, Florida Confirmed interest in being a treating center 23
Referring Centers Specialized, Targeted Sales Team Two Complementary Teams of Representatives HEPZATO Treating Center Hospital Representative Responsibilities • Manage Treating Centers Including VAC/Formulary Anesthesiologist • Support Treating Teams • Facilitate REMS Compliance Medical Medical • Generate Intra-Center Referrals Oncologist Oncologist Perfusionist Interventional Radiologist • Prospect and Open New Centers with Oncology Representative Trained Treating Team Medical Medical Oncology Representative Oncologist Oncologist Responsibilities • Generate Inter-Center Referrals • Support Hospital Rep / Generate Intra-Center Referrals • Prospect and Open New Centers with Hospital Representative 24
Reimbursement HEPZATO will be billed as a drug with a J-Code Medicare Private Payer Patients Patients • Initially a C-Code • Private Payers for rare disease generally follow Medicare guidelines and we expect these patients to be treated as outpatients • Majority of patients will be outpatient (2 midnight • Prior-Authorization of patients might be needed, we are planning to rule) with the drug directly contract out a hub service covered by Medicare • Centers of Excellence (Prospective Payment System (PPS) exempt and NCI designated Cancer Centers) have the leverage to negotiate favorable rates and reimbursement terms (our target sites are all either PPS exempt or NCI Cancer Centers) 25
PHP Is ALREADY Part of Current NCCN Guidelines for mUM Regional Isolation Perfusion Methods include isolated hepatic infusion (IHP), percutaneous hepatic perfusion (PHP), HAI, and embolization techniques. PHP is a simpler, less invasive alternative to IHP that can be repeated. It uses a double-balloon catheter inserted into the inferior vena cava to isolate hepatic venous blood that is then filtered extracorporeally. 26
Components of Hospital Reimbursement Assuming Outpatient Pass Through Status with C Code Drug Healthcare “Physician” Facility Fee payment • ASP+6% (CMS) • Highly variable based • Actually goes to hospital • Likely similar for on coding – we do not but still matters to MD commercial payers “map” to any existing CPT Code • Highly variable based code mapping complete on coding – we do not • Using existing codes “map” to any existing – while important, is advised and should code it will not have a provide the hospital • Using existing codes is meaningful impact adequate payment advised and should on drug pricing provide the hospital decision adequate payment 27
HEPZATO vs. KIMMTRAK Cost of Treatment Comparisons At First Assessment (first time to discontinue treatment because of progression) Drug Dose Cost* Treatments # Total cost Kimmtrak $19,289 24 $462,936 Hepzato t.b.d. 2 t.b.d. Mean HEPepzato treatment vs. mean treatment duration of Kimmtrak Drug Dose Cost Mean Treatments # Total cost Kimmtrak $19,289 41 $790,849 Hepzato t.b.d. 4.1 t.b.d. Annual Hepzato treatment vs. Annual treatment duration of Kimmtrak Drug Dose Cost Mean Treatments # Total cost Kimmtrak $19,289 52 $1,003,028 Hepzato t.b.d. 6 t.b.d. *Dose Cost ASP calculated using 7/2023 CMS payment allowance limit 28
Rapid Uptake for FDA Approved Treatment in mUM Kimmtrak US Quarterly Sales (USD) Demonstrated demand for FDA approved treatments for mUM 50,000,000 • KIMMTRAK - $41.7 million in Q2 2023 US sales ($167M annualized revenue) 40,000,000 • Only 45% of mUM patients are eligible for treatment with KIMMTRAK (unique MOA) 30,000,000 • KIMMTRAK captured an estimated 40% share of eligible patients within12 months 20,000,000 10,000,000 HEPZATO KIT approved August 14, 2023 to treat patients with liver dominant mUM 0 • mUM patients with liver involvement of <50% are eligible for treatment with HEPZATO Q1 Y1 Q2 Y1 Q3 Y1 Q4 Y1 Q1 Y2 Q2 Y2 • HEPZATO would require <20% of eligible patients to achieve similar 4 quarter growth* Kimmtrack US Quarterly Sales • HEPZATO has no HLA genotype restrictions and will be the only FDA approved drug for 55% of all mUM patients, as well as for KIMMTRAK failure patients % of TAM to Achieve Similar Revenue HEPZATO KIT is well positioned to capture a similar share of its TAM Growth • HEPZATO is more of a complement than a competitor to KIMMTRAK for patients eligible for KIMMTRAK 60 50 • HEPZATO EAP patients have included: 1st line stand alone treatment, 1st line treatment for those intending to receive KIMMTRAK, as 2nd line treatment, and as a 3rd line palliative treatment 40 30 • NCCN Guidelines currently state “regional isolation perfusion of the liver” as a recommended treatment 20 • “If disease is confined to the liver, regional therapies…should be considered. Since tebentafusp-tebn response 10 rates are low, symptomatic patients may be better palliated by liver-directed treatment first….” NCCN Guidelines Melanoma Uveal V1.2023 0 Q1 Y1 Q2 Y1 Q3 Y1 Q4 Y1 Q1 Y2 Q2 Y2 Kimmtrak HEPZATO KIT 29
Clinical Rationale for Broad Development Effort PHP treats the entire liver and is not dependent on Promising ORR, DCR and PFS signals seen across multiple tumor tumor location or number types with CHEMOSAT in Europe and in earlier studies with IHP of lesions HEPZATO is the only liver directed treatment which can repeatedly treat Liver mets are often the whole liver life limiting and reduce I/O efficacy Early data supports that combination with I/O agents is safe and effective Converting unresectable liver metastases into Potential for significant improvement in survival resectable 30
Strong Correlation of IHP and PHP Efficacy in mUM Patients IHP activity in CRC and NET IHP in mCRC 27 Meta-analysis of 8 mUM clinical studies ORR 50% 28 Van Iersel mPFS 7.4 months mOS 24.8 months Endpoint IHP (%) PHP (%) ORR 82% 29 Magge 1-year OS rate 91% 2-year OS rate 72% mOS 17.1 17.3 ORR 59% 30 mTTP 7.7 months Rothbart mPFS 7.2 9.6 mOS 28.8 months ORR 76% 31 Bartlett DOR 8.5 months hPFS 10 9.5 mOS 16 months IHP in mNET Complications 39.1 23.8 ORR 50% DOR 15 months 32 Grover mhPFS 7 months Mortality 5.5 1.8 mOS 48 months IHP, or Intrahepatic Perfusion, is an invasive surgical technique for delivering high doses of chemotherapy to the liver; procedure related mortality and morbidity prevented common usage. PHP is a minimally invasive, safer procedure which accomplishes the same goals as IHP and can be performed up to 6 times. 31
Chemosat Has Been Used Across Multiple Tumor Types » CE Marked - available in ~23 centers in 4 countries CHEMOSAT Used In 13 Tumor Types » Delcath resumed direct sales on 3/1/22 » ~1,400 commercial Chemosat kits shipped to the EU ~70%: Metastatic Ocular Melanoma (mUM) Other Types Treated: » Strong interest to fuel additional indications driven by • Intrahepatic Cholangiocarcinoma (ICC) HCP’s • Hepatocellular Carcinoma (HCC) » Results from over 20 retrospective and prospective • Metastatic Colorectal Cancer (mCRC) trials published by independent investigators • Metastatic Breast (mBreast) • Pancreatic • Metastatic Neuroendocrine Tumors (mNET) » NICE (UK) upgraded status from “Research” to • Metastatic Cutaneous Melanoma (mCM) “Special Status” » German reimbursement based on annual hospital special request (“ZE” process) » Broader usage pending FOCUS trial publication to support reimbursement 32
Rationale for Combining HEPZATO with IO Therapy Liver Metastases Suppress IO Therapy Efficacy 33
CHOPIN: Phase mUM 1b/2 randomized study of PHP vs PHP+IO Ipilimumab + Ipilimumab + Ipilimumab + Ipilimumab + nivolumab melphalan liver nivolumab nivolumab melphalan liver nivolumab Inclusion c1: 1+1mg/kg chemo-saturation c1: 1+1mg/kg c1: 1+1mg/kg chemo-saturation c1: 1+1mg/kg c2: 1+3mg/kg c2: 1+3mg/kg c2: 1+3mg/kg c2: 1+3mg/kg 38 • N=7 in Phase 1b portion of the trial • RP2D: IPI 1mg/kg and NIVO 3mg/kg. Well tolerated, no DLTs or deaths. • 1CR, 6 PR and 1 PD (85.7% ORR, 100% DCR) – meta-analysis of prior IO trials has shown ORR<<10% • As of 11/15/22 the median follow-up was 29.1 months, the median PFS was 29.1 months, and the median duration of response was 27.1 months. All patients are still alive. • 3 of 4 patients who subsequently experienced PD continued with treatment in the form of repeated Melphalan Chemosat treatments • Ongoing randomized Phase 2 (control is Chemosat) has recruited 50% of N=76 patients and will provide an interim analysis at N=40 patients 34 34
Market Expansion: Significant Investigator Interest 50,000 Limited, but High Liver Dominant Patients By Cancer Type* Unmet Need IHP Efficacy Well 41 Documented Combination Therapy – IO Agents 40,000 Limited, but High Unmet Need 30,000 US TAM 40 ~10 EU Cases >$1B Phase 2 Data 20,000 Extensive EU Per Year 39 Experience 10,000 FOCUS Trial 0 mOM ICC mBC mNET mPC mCRC HCC U.S. Incidence 3,4 5,6 9-12 8,9 *Metastatic Ocular Melanoma (mUM) , Cholangiocarcinoma (ICC) , Liver-dominant Breast Cancer (mBC) , Metastatic Neuroendocrine Tumors (mNET) 35 9,15 13,14 17 Metastatic Pancreatic Cancer (mPC) , Metastatic Colorectal Cancer (mCRC) , Hepatocellular carcinoma (HCC) U.S. Incidence
Multi-Disciplinary, Experienced Leadership Team JOHN PURPURA GERARD MICHEL BOARD OF DIRECTORS Chief Executive Officer Chief Operating Officer John R. Sylvester Chairman » Past VP and Exec Director roles of » 30+ yrs. pharma/medtech experience Dr. Roger G. Stoll, Ph.D. Director Reg. Affairs for Bracco Diagnostics » C-suite roles at Vericel Corp, Biodel, » Held senior roles Sanofi-Aventis, & NPS Elizabeth Czerepak Director Bolar Pharma, Luitpold Pharma & » M.S. Microbiology, B.S. Biology & Eon Labs Steven Salamon Director Geology from the Univ. of Rochester » M.S. Mgmnt. & Policy and B.S. School of Medicine Dr. Gil Aharon, Ph.D. Director Chemistry and Biology at the State » M.B.A. Simon School of Business & University of NY at Stony Brook Gerard Michel CEO Leadership KEVIN MUIR SANDRA PENNELL VOJISLAV VUKOVIC, MD PHD General Manager, Interventional Oncology SVP, Finance Chief Medical Officer » 20+ yrs. of medtech/bioTx sales & » 20+ years' biotech financial oversight » Oncology dev. exec, global clinical experience expertise marketing experience. » Manages global financial affairs, U.S. » Former CMO at Aileron, Taiho, Synta » Held senior leadership roles at BTG, ClearFlow, Aragon Surgical, Kensey GAAP compliance » MD, Univ. of Sarajevo | MSc, PhD, Nash Corporation, and Kyphon. » Led finance at Invivyd, VP at Vericel Univ. of Toronto » Field Artillery officer in the U.S. Army Corp » Published, AACR, ASCO, ASH, » B.S. in Management Systems » MSc, Accountancy, Univ. of Illinois ESMO member Engineering at the U.S. Military Academy at West Point 36
Capital Structure and Share Information DCTH (NASDAQ) Share Listing - Current a. As of June 30, 2023; includes 15.3M of Common plus 1.1M Preferred E & E-1, 2.9M of Preferred F-2 & 1.0M Pre-funded Warrants as converted a 20.3M Shares Outstanding b. As of June 30, 2023; (10-Q filing on August 9, 2023) b $14.6M Cash and Cash Equivalents c. As of June 30, 2023; 3.6M warrants at a $10 exercise price, 7.78M Tranche A warrants for an aggregate exercise price $35 million exercisable until the earlier of 3/31/2026 or 21 days receipt of FDA approval for HEPZATO; and 4.17M Tranche B warrants c 15.56M Warrants Outstanding for an aggregate exercise price $25 million exercisable until the earlier of 3/31/2026 or 21 days following recording at least $10 million in quarterly U.S. revenue. 2.9M Stock Options Granted d. Q2 Net cash used in operating activities (increase from Q1 2023 due to pay down of accrued liabilities) d $9.6M 2023 Q2 Cash Burn e. Includes $5.0M of notes convertible at $11.98 per common share equivalent, e $9.8M Debt f. Used NASDAQ closing price information starting on July 1, 2022 – June 30, 2023 f $2.59 - $7.96 52 week Low – High g. 30-day average calculated between May 18, 2023,- June 30, 2023 g 72,722 30d Average Daily Volume 37
Delcath: Investment Summary 4Q launch in mUM KIMMTRAK proving out significant commercial opportunity (~$167M run rate) with 45% of the HEPZATO TAM High penetration likely due to NCCN guidelines including PHP and equivalent OS as KIMMTRAK in more advance patient population Management team experienced in commercializing high value, specialty products Multiple 2023/2024 catalysts (Launch, CHOPIN data, Revenue Build) Potential high value follow-on indications and strategic interest creates significant upside 38
THANK YOU 39
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