On March 18, 2021 ADC Therapeutics SA (NYSE: ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, reported financial results for the fourth quarter and fiscal year ended December 31, 2020 and provided business updates (Press release, ADC Therapeutics, MAR 18, 2021, View Source [SID1234576842]).
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"The ADC Therapeutics team is well-positioned to execute on our goals for 2021 after a year of significant progress and achievements across the company in 2020," said Chris Martin, Chief Executive Officer of ADC Therapeutics. "As we approach the May 21, 2021 PDUFA date and planned commercial launch of our lead therapeutic candidate, Lonca, we have recruited a team of industry veterans to advance our commercial, medical affairs and CMC goal of rapidly bringing Lonca to patients with relapsed or refractory diffuse large B-cell lymphoma who are in desperate need of new treatment options. For our second lead program, Cami, we completed enrollment in our pivotal Phase 2 trial, bringing us one step closer to potentially addressing an unmet need in heavily pre-treated Hodgkin lymphoma patients. We look forward to reporting updated interim data from the trial in the first half of this year. Finally, we continued to develop our strong research pipeline and licensed advanced technologies for next-generation ADC research and development for patients with difficult-to-treat hematologic and solid tumor cancers."
Recent Highlights from Two Lead Programs
Loncastuximab Tesirine (Lonca)
Executing commercial strategy for mid-2021 launch in 3L+ relapsed or refractory diffuse large B-cell lymphoma (DLBCL): The Company’s commercial and medical affairs organizations are hired, trained and finalizing launch preparations in anticipation of potential U.S. Food and Drug Administration (FDA) approval in mid-2021. From a CMC perspective, the Company has commercial drug product ready for potential launch.
FDA PDUFA date set for May 21, 2021: In November 2020, the FDA accepted the Company’s Biologics License Application (BLA) filing for Lonca for the treatment of patients with relapsed or refractory DLBCL. The FDA granted priority review status for the application and has set a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2021. The BLA submission is based on data from the LOTIS 2 trial, a single-arm, open-label, 145-patient Phase 2 clinical trial of Lonca as a single agent in patients with relapsed or refractory DLBCL following ≥2 established therapies.
Initiated expanded access program (EAP) for patients in the U.S.: In January 2021, the Company initiated its EAP for Lonca for patients in the U.S. with relapsed or refractory DLBCL. The EAP is for patients who cannot be treated by currently available drugs, cell therapy, or clinical trials, and requests must be made by licensed, treating physicians in the U.S.
Presented updated Lonca clinical data at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2020: Updated data from the LOTIS 2 trial continued to demonstrate Lonca’s significant, durable antitumor activity with an overall response rate (ORR) of 48.3%, a complete response rate (CRR) of 24.8% and a median duration of response of 12.58 months. Interim data from the ongoing LOTIS 3 Phase 1/2 trial evaluating Lonca in combination with ibrutinib in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL) also showed good exposure, manageable toxicity and encouraging efficacy with an ORR of 62.9% across all patients. Lonca continued to demonstrate a manageable toxicity profile as a single agent, as well as in combination with ibrutinib.
Enrolling patients in Phase 3 LOTIS 5 clinical trial of Lonca in combination with rituximab in 2L patients: This Phase 3 confirmatory trial will evaluate the safety and efficacy of Lonca in combination with rituximab versus standard immunochemotherapy in 2L patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant. The primary endpoint will be progression-free survival. The LOTIS 5 trial would fulfill the post-marketing approval requirement with the FDA for a confirmatory study, if accelerated approval is received for relapsed or refractory DLBCL.
Expanding addressable patients for Lonca treatment: The pivotal Phase 2 trial of Lonca combined with ibrutinib has enrolled 26 of the targeted 66 non-germinal center B-cell DLBCL patients as of February 12, 2021. This trial is intended to support the submission of a supplemental BLA for Lonca in combination with ibrutinib. The Company is also expecting to initiate a pivotal Phase 2 clinical trial in follicular lymphoma (FL) in the first half of 2021. The Company plans to initiate two additional Lonca trials this year. The first trial will evaluate Lonca in combination with multiple other drugs in non-Hodgkin lymphoma (NHL). The Company also plans to initiate a dose-finding study of Lonca in combination with R-CHOP in frontline DLBCL.
Camidanlumab Tesirine (Cami)
Completed patient enrollment in pivotal Phase 2 trial: In January 2021, the Company completed enrollment in the 117-patient pivotal Phase 2 clinical trial evaluating the efficacy and safety of Cami in patients with relapsed or refractory Hodgkin lymphoma (HL).
Presented updated pivotal Phase 2 data evaluating Cami in patients with relapsed or refractory HL at the ASH (Free ASH Whitepaper) Annual Meeting in December 2020: Interim data from 51 patients in the open-label, single-arm, 117-patient pivotal Phase 2 clinical trial in patients with relapsed or refractory HL were consistent with the Phase 1 trial. Cami demonstrated encouraging antitumor activity as a single agent, with an 83% ORR, 38.3% CRR and no new safety signals.
Announced first patient dosed in combination with pembrolizumab in ongoing Phase 1b trial in selected advanced solid tumors: In October 2020, the Company dosed its first patient with Cami in combination with pembrolizumab, a checkpoint inhibitor, in an ongoing Phase 1b clinical trial in patients with selected advanced solid tumors. The multicenter, open-label, dose-escalation and dose-expansion Phase 1b trial is evaluating the safety, tolerability, pharmacokinetics and antitumor activity of Cami in combination with pembrolizumab. Pharmacokinetic and biomarker data from the Phase 1b trial were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020, and preclinical data were published in the Journal for ImmunoTherapy of Cancer.
Recent Business Updates
Preparing state-of-the-art ADC research center at the Imperial College Translation & Innovation Hub (I-HUB): In January 2021, the Company entered into an agreement to open a new state-of-the-art ADC research center for ADC Therapeutics in Imperial College’s new Translation & Innovation Hub (I-HUB) in central London. The research center will enable further platform and pipeline innovation for the Company and is expected to open in the summer of 2021.
Formed Overland ADCT BioPharma to develop and commercialize Lonca, ADCT-601, ADCT-602 and ADCT-901 in greater China and Singapore: In December 2020, the Company announced the launch of Overland ADCT BioPharma (CY) Limited (Overland ADCT BioPharma) in partnership with Hillhouse-backed Overland Pharmaceuticals to develop and commercialize four of ADC Therapeutics’ ADC product candidates for difficult-to-treat hematologic and solid tumors in greater China and Singapore. Under the terms of the agreement, ADC Therapeutics licensed exclusive development and commercialization rights to Lonca, ADCT-602, ADCT-601 and ADCT-901 for greater China and Singapore to Overland ADCT BioPharma. ADC Therapeutics received a 49% stake in the company and may also earn milestone payments and royalties. Overland Pharmaceuticals invested $50 million to fund operations. The Board of Directors includes an equal number of nominees from ADCT and Overland.
Cash balance of $439.2 million as of December 31, 2020.
2021 Expected Milestones
PDUFA target date for Lonca is May 21, 2021 and the Company is on track to launch quickly following approval (if and when received).
Initiate a pivotal Phase 2 trial of Lonca in FL in the first half of 2021.
Report updated data from the Phase 1 trial of Lonca in combination with ibrutinib in relapsed or refractory DLBCL in the first half of 2021, as well as complete enrollment in the pivotal Phase 2 expansion in the first half of this year.
Initiate dose finding study of Lonca in first-line with R-CHOP in the first half of 2021.
Report data from the 20-patient safety run-in of LOTIS 5, the Phase 3 confirmatory study of Lonca in combination with rituximab, in the second half of 2021.
Report interim results from the pivotal Phase 2 trial of Cami in HL in the first half of 2021.
Initiate a Phase 1b combination study of ADCT-601, targeting AXL, in multiple solid tumors in the second half of 2021.
File Investigational New Drug (IND) application for ADCT-901, targeting KAAG1, in the first half of 2021.
Fourth Quarter and Full Year 2020 Financial Results
Cash and Cash Equivalents
Cash and cash equivalents were $439.2 million as of December 31, 2020, compared to $115.6 million as of December 31, 2019.
Research and Development (R&D) Expenses
R&D expenses were $48.6 million for the quarter and $142.0 million for the full year ended December 31, 2020, compared to $30.4 million and $107.5 million for the same quarter and year-end 2019. R&D expenses increased as we continue to expand the potential market opportunities for Lonca in earlier lines of therapies and multiple indications, advance Cami to support BLA submission, and build our pipeline. As a result of these initiatives, employee headcount and share-based compensation increased.
Selling and Marketing (S&M) Expenses
During the fourth quarter of 2020, the Company began to present S&M expenses as a separate line item in its Consolidated Statement of Operation in anticipation for its commercial launch of Lonca. S&M expenses were $9.4 million for the quarter and $22.1 million for the full year ended December 31, 2020. The Company did not incur a material amount of S&M expenses, which were classified within general and administrative expenses, during the quarter and full year ended December 31, 2019. The increase in S&M expenses related to the build-out of the Company’s commercial organization and preparation activities for the anticipated launch of Lonca in 2021.
General and Administrative (G&A) Expenses
G&A expenses were $20.1 million for the quarter and $55.1 million for the full year ended December 31, 2020, compared to $5.3 million and $14.2 million for the same quarter and year-end 2019. The increase was primarily due to increased share-based compensation expense and costs of being a public company.
Net Loss and Adjusted Net Loss
Net loss was $55.9 million, or a net loss of $0.73 per basic and diluted share, for the quarter and $246.3 million, or a net loss of $3.77 per basic and diluted share, for the full year ended December 31, 2020, compared to $35.3 million, or a net loss of $0.69 per basic and diluted share, and $116.5 million, or a net loss of $2.36 per basic and diluted share, for the same quarter and year-end 2019. Net loss included share-based compensation expense of $15.4 million for the quarter and $42.9 million for the full year ended December 31, 2020, compared to $0.8 million and $1.1 million for the same quarter and year-end 2019. The Company recognized a gain of $24.5 million during the quarter and full year ended December 31, 2020 related to its contribution of intellectual property for its equity interest in the Overland ADCT BioPharma joint venture. The net loss for the full year ended December 31, 2020 includes a non-cash charge of $45.4 million related to the changes in fair value of derivatives associated with the convertible loans under the Facility Agreement with Deerfield. The year-to-date increase in fair value was driven by the increase in the Company’s share price from its initial public offering.
Adjusted net loss was $63.0 million, or an adjusted net loss of $0.82 per basic and diluted share, for the quarter and $176.1 million, or an adjusted net loss of $2.69 per basic and diluted share, for the full year ended December 31, 2020, compared to $34.5 million, or an adjusted net loss of $0.68 per basic and diluted share, and $115.4 million, or an adjusted net loss of $2.34 per basic and diluted share, for the same quarter and year-end 2019. The increase in adjusted net loss was primarily driven by higher employee headcount across the organization, costs associated with the expanding clinical portfolio and the preparation for the anticipated launch of Lonca in 2021.
Conference Call Details
ADC Therapeutics management will host a conference call and live audio webcast to discuss fourth quarter and full-year 2020 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the live call, please dial 833-303-1198 (domestic) or +1-914-987-7415 (international) and provide conference ID 4985202. A live webcast of the presentation will be available under "Events and Presentations" in the Investors section of the ADC Therapeutics website at ir.adctherapeutics.com. The archived webcast will be available for 30 days following the call.