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ADC Therapeutics Reports Third Quarter 2020 Financial Results and Provides Recent Business Highlights

On November 12, 2020 ADC Therapeutics SA (NYSE: ADCT), a late clinical-stage oncology-focused biotechnology company pioneering the development and commercialization of highly potent and targeted antibody drug conjugates (ADCs) for patients with hematological malignancies and solid tumors, reported financial results for the third quarter ended September 30, 2020 and provided recent business highlights (Press release, ADC Therapeutics, NOV 12, 2020, View Source [SID1234570825]).

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"The third quarter was one of tremendous execution as we prepare for the U.S. launch of our first drug, Lonca, for the treatment of relapsed or refractory diffuse large B-cell lymphoma," said Chris Martin, Chief Executive Officer of ADC Therapeutics. "We have submitted our Biologics License Application to the U.S. Food and Drug Administration and are now working diligently to prepare for a planned commercial launch in mid-2021, including U.S. organizational build-out, the establishment of U.S. operations to ensure distribution, access and reimbursement of Lonca, and significant appropriate physician engagement. In addition to our commercial preparations, we are expanding our Lonca development activities, having initiated our Phase 3 LOTIS 5 clinical trial evaluating Lonca in combination with rituximab as a second-line therapy in DLBCL and are preparing to initiate our Phase 2 trial of Lonca in follicular lymphoma next year."

Dr. Martin continued, "Across our Cami programs, we have now enrolled more than half of the 100-patient pivotal Phase 2 trial in Hodgkin lymphoma and continue to see promising preliminary data from our Phase 1b trial in solid tumors that show robust immune activity following treatment, as well as recently published preclinical data highlighting the anti-tumor activity of CD25-targeted antibody drug conjugates. With these promising data, we expanded our Phase 1b trial to evaluate Cami in combination with pembrolizumab to better understand its potential as both a monotherapy and in combination and have dosed the first patient in the combination arm. To support these exciting developments and ensure continued growth across our pipeline, we completed an upsized public offering in September. With these additional funds, we look forward to continuing to deliver on our vision to bring transformative therapies to cancer patients as quickly and effectively as possible."

Recent Clinical and Business Highlights:

Submitted a BLA to the FDA for Lonca for treatment of relapsed or refractory DLBCL: On September 21, 2020, the Company announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for Lonca for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The submission is based on data from LOTIS 2, a pivotal Phase 2 multi-center, open-label, single-arm clinical trial evaluating the efficacy and safety of Lonca in patients with relapsed or refractory DLBCL following two or more lines of prior systemic therapy.
Opened Phase 3 LOTIS 5 clinical trial of Lonca in combination with rituximab for enrollment: This Phase 3 confirmatory trial will evaluate the efficacy of Lonca in combination with rituximab in patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant (ASCT). The trial will evaluate the safety and efficacy of Lonca in combination with rituximab versus standard immunochemotherapy, and the primary endpoint will be progression-free survival. LOTIS 5 is designed to fulfill the Company’s post-marketing requirement to the FDA for full approval, if accelerated approval is received for relapsed or refractory DLBCL, and is intended to support a supplemental Biologics License Application (sBLA) for Lonca as a second-line therapy for patients with DLBCL who have relapsed or refractory disease following at least one multi-agent systemic treatment regimen.
Actively enrolling patients in the pivotal Phase 2 portion of LOTIS 3 clinical trial of Lonca in combination with ibrutinib: Enrollment continues in the pivotal Phase 2 portion of LOTIS 3, a 161-patient Phase 1/2 clinical trial of Lonca in combination with ibrutinib, which is being evaluated in patients with relapsed or refractory DLBCL or mantle cell lymphoma (MCL). The first patient was dosed in the pivotal Phase 2 portion of this trial in July 2020.
Planning to initiate a pivotal Phase 2 clinical trial of Lonca in follicular lymphoma (FL) in H1 2021: The Company continues to consider rapid expansion opportunities for Lonca across other non-Hodgkin lymphoma indications. Following consultation with the FDA, the Company plans to initiate a pivotal Phase 2 trial to evaluate the safety and efficacy of Lonca in patients with relapsed or refractory FL.
Dosed first patient in Phase 1b clinical trial of Cami in combination with pembrolizumab for treatment of solid tumors: Earlier this month, the Company announced that the first patient was dosed with Cami in combination with pembrolizumab, a checkpoint inhibitor, in an ongoing Phase 1b trial in patients with selected advanced solid tumors. Based on preclinical data and initial pharmacodynamic data from the Phase 1b monotherapy trial, the Company has expanded the Phase 1b trial to evaluate the safety, tolerability, pharmacokinetics and antitumor activity of Cami in combination with pembrolizumab in select solid tumors. 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.
Announced multiple abstracts accepted for presentation at ASH (Free ASH Whitepaper): The Company announced earlier in November that six clinical abstracts and two preclinical abstracts have been accepted for presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, including an oral presentation of Cami Phase 2 data in Hodgkin lymphoma (HL) and poster presentations of Lonca subgroup data from the pivotal Phase 2 LOTIS 2 trial in relapsed or refractory DLBCL and the Phase 1b pivotal trial of Lonca combined with ibrutinib in relapsed or refractory DLBCL and MCL.
Amended 2013 collaboration and license agreement with Genmab for Cami: In October 2020, the Company and Genmab agreed to amend their original 2013 agreement to allow the Company to continue the development and commercialization of Cami. Under the amendment, Genmab agreed, among other things, to convert its economic interest into a mid-to-high single-digit royalty on net sales.
Completed upsized public offering: In September 2020, the Company completed an upsized public offering of 6,000,000 common shares at a price of $34.00 per share. Gross proceeds from the public offering, before deducting underwriting discounts and commissions and offering expenses payable by the Company, were approximately $204 million.
Anticipated Upcoming Milestones:

FDA feedback on BLA submission for Lonca for the treatment of patients with relapsed or refractory DLBCL.
Initiation of a pivotal Phase 2 trial of Lonca in relapsed refractory FL in the first half of 2021.
Reporting of interim results from the pivotal Phase 2 trial of Cami in HL in the first half of 2021.
Potential FDA approval and launch of Lonca in mid-2021.
Third Quarter 2020 Financial Results

Cash and Cash Equivalents

Cash and cash equivalents were $494.4 million as of September 30, 2020, compared to $115.6 million as of December 31, 2019.

Research and Development (R&D) Expenses

R&D expenses were $32.2 million for the quarter ended September 30, 2020, compared to $30.5 million for the same quarter in 2019. The increase was primarily due to increased share-based compensation expense.

General and Administrative (G&A) Expenses

G&A expenses were $20.3 million for the quarter ended September 30, 2020, compared to $2.3 million for the same quarter in 2019. The increase was primarily due to an increased number of Commercial employees, increased costs due to new commercial activities and increased share-based compensation expense.

Net Loss and Adjusted Net Loss

Net loss was $20.3 million, or a net loss of $0.29 per basic and diluted share, for the quarter ended September 30, 2020, compared to $31.3 million, or a net loss of $0.62 per basic and diluted share, for the same quarter in 2019. The net loss for the quarter ended September 30, 2020 includes a $33.9 million non-cash gain related to the changes in fair value of derivatives associated with the convertible loans under the Convertible Credit Facility with Deerfield. The decrease in fair value was driven by the decrease in the Company’s share price from June 30, 2020. In addition, net loss included share-based compensation expense of $11.0 million for the quarter ended September 30, 2020, compared to $0.2 million for the same quarter in 2019.

Adjusted net loss was $41.3 million, or an adjusted net loss of $0.58 per basic and diluted share, for the quarter ended September 30, 2020, compared to $31.1 million, or an adjusted net loss of $0.62 per basic and diluted share, for the same quarter in 2019. The increase in adjusted net loss was primarily driven by higher employee headcount across the organization and costs associated with the build out of the Company’s commercial organization in 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 third quarter 2020 financial results and provide a company update today at 8:30 a.m. Eastern Time. To access the call, please dial +41 225 675632 (international) or (833) 249-8403 (U.S.). A live webcast of the presentation will be available on the Investors section of the ADC Therapeutics website at www.ir.adctherapeutics.com. The archived webcast will be available after the completion of the event.

SQZ Biotech to Present at November Virtual Investor Conferences

On November 12, 2020 SQZ Biotechnologies (NYSE: SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas, reported that Armon Sharei, PhD, chief executive officer of SQZ, and additional management will participate in the following upcoming virtual investor conferences (Press release, SQZ Biotech, NOV 12, 2020, View Source [SID1234570824]):

Stifel 2020 Virtual Healthcare Conference
Tuesday, November 17, 2020
Presentation Time: 1:20 pm EST
Webcast available

Jefferies Virtual London Healthcare Conference
Thursday, November 19, 2020
Presentation Time: 7:55 am EST/12:55 pm GMT
Webcast available

The live webcast of SQZ’s presentations can also be accessed through the "Events & Presentations" page within the Investors & Media section of the SQZ website. Replays of the webcast will be available on the SQZ website for 90 days following the event.

Atara Biotherapeutics Presents New Preclinical Data on ATA3271, a Next-Generation Allogeneic Mesothelin-Targeted CAR T to Treat Solid Tumors, at the 35th Society for Immunotherapy of Cancer Annual Meeting (SITC 2020)

On November 12, 2020 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a pioneer in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with serious diseases including solid tumors, hematologic cancers and autoimmune disease, reported the presentation of the first preclinical evaluation of ATA3271, a next-generation, off-the-shelf, allogeneic EBV CAR T-cell therapy targeting mesothelin designed for the treatment of solid tumors (Press release, Atara Biotherapeutics, NOV 12, 2020, View Source [SID1234570823]). These data are being featured in a poster presentation at the 35th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (SITC 2020), November 11-14, 2020.

"We have made meaningful progress advancing IND-enabling studies for ATA3271, an allogeneic mesothelin CAR T, which leverages our differentiated EBV T-cell platform and utilizes the PD1DNR and 1XX technologies to improve efficacy, persistence, and durability of response. Such innovative CAR T design addresses key hurdles for realizing the potential for CAR T therapies in solid tumor settings," said Jakob Dupont, Global Head of Research and Development at Atara. "Mesothelin, an antigen associated with aggressive solid tumors, is a promising target for tumor-specific therapy and combined with our EBV T-cell platform and the PD1DNR and 1XX technologies has led to the potent preclinical antitumor activity of ATA3271 that functionally persists after multiple tumor cell challenges."

Results presented at SITC (Free SITC Whitepaper) detail findings from in vitro and in vivo evaluation of ATA3271. Specifically, in vitro functional studies show potent antitumor activity of ATA3271 against mesothelin-expressing cell lines, with potency maintained in the presence of high tumor PD-L1 expression. These data support the design of ATA3271, which expresses a dominant negative version of PD-1 receptor, to maintain function in the presence of suppressive checkpoint ligands commonly associated with solid tumor microenvironments. In addition, results further support the combined functional design of ATA3271’s 1XX costimulatory domain technology in maintaining memory phenotype while limiting cell exhaustion in the context of repeated tumor cell challenges.

Furthermore, ATA3271 retains reduced allocytotoxic function against HLA mismatched targets, a characteristic that is associated with Atara’s allogeneic EBV T-cell platform that leverages enrichment of endogenous EBV-TCR function to decrease clinical risks for GvHD. We also believe that our allogeneic EBV CAR T-cell platform may prevent cellular exhaustion and augment in vivo expansion.

In vivo, ATA3271 exhibited potent antitumor activity and significant survival benefit in mice implanted with MGM-PDL1 cells that highly express both mesothelin as well as PD-L1. This in vivo potency was demonstrated without evident toxicities. All mice treated with ATA3271 (n=10) survived through the study duration, while control mice (n=10) all died within a median duration of 25 days (15- to 35-day survival range), post tumor implantation. Evidence in six of ten mice also showed that ATA3271 persisted in vivo by day 51. Ex vivo analysis of a subset of these persistent cell populations (n=4) demonstrated maintenance of phenotypic memory markers over the duration of the in vivo activity.

Mesothelin is a tumor-specific antigen that is commonly expressed at high levels on the cell surface in many aggressive solid tumors including mesothelioma, triple-negative breast cancer, esophageal cancer, ovarian cancer, pancreatic cancer and non-small cell lung cancer and is an attractive target for immune-based therapies. Both in vitro and in vivo results for ATA3271 suggest that allogeneic mesothelin-CAR-engineered EBV T cells are a promising approach for the treatment of mesothelin-positive cancers.

"The results presented today further support the continued development of our allogeneic mesothelin-targeted next-generation CAR T program," said AJ Joshi, M.D., Senior Vice President and Chief Medical Officer at Atara. "We look forward to building upon these foundational preclinical studies to advance ATA3271 in the clinic with the goal of bringing a potentially transformative therapeutic option to treat aggressive solid tumors including mesothelioma."

Atara’s next generation CAR T immunotherapy franchise for mesothelin also includes autologous ATA2271. The U.S. Food and Drug Administration (FDA) recently accepted an Investigational New Drug (IND) application to initiate a Phase 1 clinical study of ATA2271 for the treatment of advanced mesothelioma.

Provectus Biopharmaceuticals Announces Acceptance of PV-10® Melanoma Abstract for Oral Presentation at Melanoma Bridge 2020

On November 12, 2020 Provectus (OTCQB: PVCT) reported that data from the Company’s ongoing Phase 1b/2 study of autolytic cancer immunotherapy PV-10, an injectable formulation of Provectus’ proprietary small molecule rose bengal disodium (RBD), in combination with KEYTRUDA (pembrolizumab) for the treatment of advanced cutaneous melanoma in patients refractory to immune checkpoint blockade (CB) will be presented at Melanoma Bridge 2020, to be held online from December 3-5, 2020 .

The abstract accepted for oral presentation is entitled "Response for combination of PV-10 autolytic immunotherapy and immune checkpoint blockade in checkpoint-refractory patients."

Intralesional (IL) (aka intratumoral) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death and induce tumor-specific reactivity in circulating T cells.1,2,3 This IL PV-10-induced functional T cell response may be enhanced and boosted in combination with CB.4 In CB-refractory advanced cutaneous melanoma, IL PV-10 may restore disease-specific T cell function, which may also be prognostic of clinical response.

About the Phase 1b/2 Combination Therapy Trial (NCT02557321)

A first expansion cohort of the Phase 1b portion of the study began enrolling patients with metastatic cutaneous melanoma who were CB-refractory in December 2018. This CB-Refractory Cohort extended an exploratory group of refractory patients enrolled into the study’s main cohort that primarily enrolled CB-naïve patients. Patients with at least one injectable lesion and who were candidates for KEYTRUDA were eligible. Eligible subjects received the combination treatment of PV-10 and KEYTRUDA every three weeks for up to five cycles (i.e., over a period of up to 12 weeks), followed by only KEYTRUDA every three weeks for up to 24 months. The protocol allows for additional cycles of PV-10 beyond the fifth cycle for patients with additional injectable disease. The primary endpoint for the Phase 1b trial was safety and tolerability. ORR and progression-free survival were key secondary endpoints (both assessed via RECIST 1.1 after five treatment cycles, and then every 12 weeks thereafter).

About Rose Bengal Disodium

RBD is 4,5,6,7-tetrachloro-2′,4′,5′,7′-tetraiodofluorescein disodium, a halogenated xanthene and Provectus’ proprietary lead molecule. Provectus’ current Good Manufacturing Practices (cGMP) RBD is a proprietary pharmaceutical-grade drug substance produced by the Company’s quality-by-design (QbD) manufacturing process to exacting regulatory standards that avoids the formation of uncontrolled impurities currently present in commercial-grade rose bengal. Provectus’ RBD and cGMP RBD manufacturing process are protected by composition of matter and manufacturing patents as well as trade secrets.

An IL formulation (i.e., by direct injection) of cGMP RBD drug substance, cGMP PV-10, is being developed as an autolytic immunotherapy drug product for solid tumor cancers. By targeting tumor cell lysosomes, RBD treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells, including a T cell mediated immune response against treatment refractory and immunologically cold tumors.1,2,3 Adaptive immunity can be enhanced by combining CB with RBD.4 IL PV-10 is undergoing clinical study for relapsed and refractory adult solid tumor cancers, such skin and liver cancers.

IL PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers, such as neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.5,6

A topical formulation of cGMP RBD drug substance, PH-10, is being developed as a clinical-stage immuno-dermatology drug product for inflammatory dermatoses, such as atopic dermatitis and psoriasis. RBD can modulate multiple interleukin and interferon pathways and key cytokine disease drivers.7

Oral formulations of cGMP RBD are undergoing preclinical study for relapsed and refractory pediatric blood cancers, such as acute lymphocytic leukemia and acute myelomonocytic leukemia.8,9

Oral formulations of cGMP RBD are also undergoing preclinical study as prophylactic and therapeutic treatments for high-risk adult solid tumor cancers, such as head and neck, breast, pancreatic, liver, and colorectal cancers.

Different formulations of cGMP RBD are also undergoing preclinical study as potential treatments for multi-drug resistant (MDR) bacteria, such as Gram-negative bacteria.

Tumor Cell Lysosomes as the Seminal Cancer Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.10 Cancer progression and metastasis are associated with lysosomal compartment changes11,12, which are closely correlated (among other things) with invasive growth, angiogenesis, and drug resistance13.

RBD selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus1,14, external collaborators5, and other researchers15,16,17 have independently shown that RBD triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via RBD: RBD-induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the process (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames, with a duration of approximately one hour). Exposure to RBD triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video of the process, with a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to RBD.5

Tumor Autolytic Death via RBD: RBD causes acute autolytic destruction of injected tumors (via autolytic cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens; release of these signaling factors may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity.9

Orphan Drug Designations (ODDs)

ODD status has been granted to RBD by the U.S. Food and Drug Administration for metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Intellectual Property (IP)

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which cGMP RBD and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial-grade rose bengal in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of RBD and CB (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942.

Kadmon to Present at Upcoming Investor Conferences

On November 12, 2020 Kadmon Holdings, Inc. (NASDAQ:KDMN) reported that Harlan W. Waksal, M.D., President and Chief Executive Officer, will present at the following virtual investor conferences (Press release, Kadmon, NOV 12, 2020, View Source [SID1234570820]):
Jefferies Virtual London Healthcare Conference

Date: Wednesday, November 18, 2020
Time: 12:35 p.m. ET
Evercore ISI 3rd Annual HealthCONx Virtual Conference

Date: Thursday, December 3, 2020
Time: 8:00 a.m. ET
Live audio webcasts of the presentations may be accessed on the Investors section of the Kadmon website at www.kadmon.com. Replays of the webcasts will be available for 90 days.