Elpiscience Announces FDA IND Clearance of ES014, a First-in-Class Anti-CD39xTGF-β Bispecific Antibody for Patients with Advanced Solid Tumors

On May 9, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported that the U.S. Food and Drug Administration (FDA) has cleared Elpiscience’s ES014 Investigational New Drug (IND) Application to initiate a Phase 1 clinical study for patients with advanced solid tumors (Press release, Elpiscience, MAY 9, 2022, View Source [SID1234613964]). ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody (bsAb) that simultaneously targets the CD39-adenosine and TGF-β pathways, two major immunosuppressive mechanisms in the tumor microenvironment (TME).

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"We are delighted that our IND for ES014 was cleared by FDA," said Steve Chin, Chief Medical Officer of Elpiscience. "ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody. In preclinical studies, ES014 demonstrated significant anti-tumor activity in a PD-1 resistant in vivo efficacy model. We look forward to starting the Phase 1 study soon."

Solid tumors frequently express TGF-β, which suppresses T cell activation and induces CD39 expression, the rate-limiting enzyme in the ATP-adenosine pathway​. The anti-CD39 target is designed to selectively direct ES014 to the TME where the anti-TGF-β activity promotes effector T cell function and immune activation, while avoiding or minimizing systemic immunotoxicity. ES014’s anti-CD39 activity further aims to reverse TME immunosuppression by reducing suppressive adenosine, while maintaining high levels of immune-stimulatory extracellular ATP. The combined removal of immune suppression and immune stimulating effects of ES014 were recently demonstrated in a PD-1 antibody non-responsive in vivo animal model where tumor growth was significantly inhibited after treatment.

ADC Therapeutics Reports First Quarter 2022 Financial Results and Provides Business Updates

On May 9, 2022 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, reported financial results for the first quarter ended March 31, 2022 and provided business updates (Press release, ADC Therapeutics, MAY 9, 2022, View Source [SID1234613963]).

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"ZYNLONTA continues to extend its reach in the DLBCL market with its differentiated product profile and broad applicability across the 3L+ patient population. We are pleased by the team’s progress since launch in bringing ZYNLONTA to patients. Sales in the first quarter were unfavorably impacted by the customer inventory build at the end of last year and fewer new patient starts in the DLBCL market in the first quarter, which was exacerbated by the Omicron surge," said Chris Martin, DPhil, former Chief Executive Officer of ADC Therapeutics. "We have a strong clinical development program to potentially expand ZYNLONTA’s use into earlier lines of therapy, and we are also excited about our promising portfolio of solid tumor programs. We look forward to providing updates as they become available."

Recent Highlights and Developments

Corporate Update

Today, Chris Martin has transitioned the role of Chief Executive Officer to Ameet Mallik. Dr. Martin will serve as a non-executive member of the Board of Directors and Chair of the Science and Technology Committee. He will also serve as an advisor to the Company for the next three months to ensure a smooth transition.
Hematology Franchise

ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA generated net sales of $16.5 million in the first quarter of 2022, reflecting a modest fourth quarter customer inventory build and fewer new patient starts in the diffuse large B-cell lymphoma (DLBCL) market in 1Q 2022, which was exacerbated by the Omicron surge.
ZYNLONTA awareness and familiarity continues to increase and ZYNLONTA share of voice is performing well in the relapsed/refractory DLBCL market. Market share in the 3L+ setting is also increasing.
In terms of account penetration, 96% of priority accounts have ordered ZYNLONTA since launch and 94% of National Comprehensive Cancer Network centers have ordered ZYNLONTA since launch.
The permanent J-code for ZYNLONTA (J9359) was issued by the U.S. Centers for Medicare & Medicaid Services and took effect April 1, 2022.
The Phase 3 LOTIS-5 trial in combination with rituximab in second-line transplant-ineligible DLBCL patients continues to enroll the randomized portion of the trial.
The Overland ADCT BioPharma joint venture continues to make progress in China and enrollment continues in the local pivotal Phase 2 trial of ZYNLONTA in relapsed or refractory (r/r) DLBCL.
The Company is actively engaged with its partner Mitsubishi Tanabe Pharma Corporation (MTPC) in Japan to develop ZYNLONTA in DLBCL.
Cami (camidanlumab tesirine) in Hodgkin lymphoma (HL)

The 12-month patient follow-up in this pivotal Phase 2 trial has been completed. The Company has submitted the data to an upcoming oncology conference.
Solid Tumor Franchise

Cami (targeting CD25)

The Company is concurrently advancing the dose escalation and a dose expansion cohort of the Phase 1b trial of Cami in combination with pembrolizumab. The Company has initiated a limited expansion at 60 µg/kg based on investigator observation of stable disease or tumor response, and the dose escalation continues at 100 µg/kg.
Upcoming Expected Milestones

Hematology Franchise

ZYNLONTA

Continue to enroll the randomized portion of the LOTIS-5 confirmatory trial in combination with rituximab in second-line transplant-ineligible DLBCL patients
Initiate the LOTIS-7 trial in multiple combinations in non-Hodgkin lymphoma in 1H 2022
Initiate the LOTIS-9 trial in combination with rituximab in first-line unfit/frail DLBCL patients in 2H 2022
Cami

Report topline results for the pivotal Phase 2 trial in HL in 1H 2022
Meet with FDA for pre-BLA meeting in 2H 2022
ADCT-602 (targeting CD22)

Continue to enroll the Phase 1 trial in acute lymphoblastic leukemia (ALL)
Solid Tumor Franchise

Cami (targeting CD25)

Continue to advance the Phase 1b solid tumor trial of Cami in combination with pembrolizumab, with safety and efficacy data anticipated in 2023
ADCT-901 (targeting KAAG1)

Continue to enroll the Phase 1 trial in multiple solid tumors, with safety and efficacy data anticipated in 2023
ADCT-601 (targeting AXL)

Initiate the Phase 1b combination trial in multiple solid tumors in 1H 2022
ADCT-701 (targeting DLK1)

Continue to work with the National Cancer Institute to complete preclinical studies to support an IND filing
ADCT-212 (targeting PSMA)

Continue completion of preclinical studies to support an IND filing
First Quarter Financial Results

Product Revenue

Product revenue (net) was $16.5 million for the quarter, compared to zero for the same quarter in 2021. Net revenues are for U.S. sales of ZYNLONTA, which received accelerated approval from the FDA on April 23, 2021.

Cash and Cash Equivalents

Cash and cash equivalents were $430.9 million as of March 31, 2022, compared to $466.5 million as of December 31, 2021.

Research and Development (R&D) Expenses

R&D expenses were $49.0 million for the quarter ended March 31, 2022, compared to $39.2 million for the same quarter in 2021. R&D expense increased for the quarter ended March 31, 2022, as compared to the same quarter in 2021 as a result of increased investment in programs to evaluate ZYNLONTA in earlier lines of therapy and our broad portfolio.

Selling and Marketing (S&M) Expenses

S&M expenses were $18.4 million for the first quarter ended March 31, 2022, as compared to $13.9 million for the same quarter in 2021. The increase in S&M expenses are related to the ongoing launch of ZYNLONTA.

G&A Expenses

G&A expenses were $19.0 million for the quarter ended March 31, 2022, compared to $17.6 million for the same quarter in 2021. G&A expenses increased primarily due to professional fees associated with the MTPC license agreement in Japan.

Net Loss and Adjusted Net Loss

Net loss was $16.7 million, or a net loss of $0.22 per basic and diluted share, for the quarter ended March 31, 2022. This compares to a net loss of $51.5 million, or a net loss of $0.67 per basic and diluted share, for the same quarter in 2021.

Adjusted net loss was $27.7 million, or an adjusted net loss of $0.36 per basic and diluted share, for the quarter ended March 31, 2022. This compares to $56.8 million, or an adjusted net loss of $0.74 per basic and diluted share, for the same quarter in 2021.

The decrease in net loss and adjusted net loss for the quarter ended March 31, 2022, as compared to the same period in 2021, was primarily due to license revenue of $30 million arising from the MTPC agreement, partially offset by the increase in R&D and S&M expenses. In addition, net loss decreased for the first quarter of 2022 as a result of income arising from a cumulative catch-up adjustment associated with the valuation of the deferred obligation with Healthcare Royalty Partners, partially offset by higher interest expense associated with the Deerfield credit facility and deferred obligation, both of which are excluded from adjusted net loss.

Conference Call Details

ADC Therapeutics management will host a conference call and live audio webcast to discuss first quarter 2022 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 6928367. A live webcast of the presentation will be available under "Events & 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.

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

ADC Therapeutics Announces CEO Transition

On May 9, 2022 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, reported that Chris Martin, DPhil, has stepped down as Chief Executive Officer (Press release, ADC Therapeutics, MAY 9, 2022, View Source [SID1234613962]). Dr. Martin will serve as a non-executive member of the Company’s Board of Directors and Chair of the Science and Technology Committee. He will also serve as an advisor to the Company for the next three months to ensure a seamless transition. ADC Therapeutics is pleased to announce that Ameet Mallik has been appointed as its new Chief Executive Officer. He will be based from ADC Therapeutics’ office in New Providence, New Jersey.

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"Since co-founding ADC Therapeutics in 2011, I have had the privilege of taking our proprietary ADC technology from discovery to the bench to our first FDA approval of ZYNLONTA," said Dr. Martin. "The Company has grown from a private startup to a New York Stock Exchange-listed company with over 300 employees and a commercial product addressing an unmet need in diffuse large B-cell lymphoma patients. In addition, the Company’s pipeline includes Cami, which is progressing towards a BLA submission, five promising solid tumor programs in development and a strong ADC platform and R&D pipeline. The approval and successful launch of ZYNLONTA was a particular highlight for me. With the Company and its pipeline in such a strong position, I am very pleased to be passing the baton to Ameet Mallik, whose deep commercial oncology experience and proven leadership qualities will drive the Company through its next chapter of growth. I look forward to partnering with Ameet to ensure a smooth transition and continuing to be a steward of the Company serving on the Board."

Ameet Mallik’s pharmaceutical career was highlighted by 16 years at Novartis, most recently as Executive Vice President and Head of U.S. Oncology. Prior to that, he held various leadership roles at Novartis Oncology including Head of Global Marketing, Value and Access and Head of Latin America and Canada. He also served as Global Head of Biopharmaceuticals and Oncology injectables at Sandoz, a division of the Novartis Group, and Head of Global Strategic Planning at Novartis Pharmaceuticals. Prior to Novartis, Mr. Mallik was an Associate Principal at McKinsey & Company. Most recently, Mr. Mallik served as CEO of Rafael Holdings, a biotech company focused on developing oncology and immune therapies. He serves on the Boards of Atara Biotherapeutics and Rafael Holdings. Mr. Mallik holds an M.B.A. from The Wharton School at the University of Pennsylvania, and an M.S. in Biotechnology and B.S. in Chemical Engineering, both from Northwestern University.

Mr. Mallik commented, "I am thrilled to join the ADC Therapeutics team and build on its solid foundation. I was drawn to the Company’s strong team and culture, its validated technology platform, a differentiated commercial product in ZYNLONTA, a portfolio of promising assets and an impressive research engine. It is truly remarkable what Dr. Martin and the ADC Therapeutics team have achieved in such a short period of time since the Company’s founding in 2011. It is a privilege to lead the Company through its next phase of growth, with the potential to create sustainable value for all of our stakeholders."

"On behalf of the Board of Directors, I would like to sincerely thank Chris for his many contributions to ADC Therapeutics over the last 11 years. His two decades of experience as a pioneer in the ADC space have been instrumental in building the Company, and he will be invaluable in his continued role on the Board," said Ron Squarer, Chairman of the Board of Directors of ADC Therapeutics. "I am delighted to welcome Ameet Mallik to the role of Chief Executive Officer. At this important juncture as the Company has transitioned to a fully-integrated research, development and commercial organization, I am confident that Mr. Mallik’s strong commercial background and strategic vision for the Company will lead ADC Therapeutics to bring leading-edge new therapies for patients suffering from cancer."

Bio-Thera Solutions Announces First Patient Dosed in Australia for BAT7104, a Bispecific Antibody Targeting PD-L1 and CD47 for the Treatment of Advanced Solid Tumors

On May 9, 2022 Bio-Thera Solutions, Ltd. (SH: 688177), a commercial-stage pharmaceutical company, reported that dosing has begun in a Phase 1 clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of BAT7104, a bispecific antibody that specifically blocks the interaction of human PD-L1 and CD47 with their corresponding receptors (Press release, BioThera Solutions, MAY 9, 2022, View Source [SID1234613960]).

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BAT7104 was designed to inhibit the PD-1/PD-L1 and CD47/SIRP-α pathways. By an "imbalanced" design with finely tuned binding affinity to CD47 and high affinity to PD-L1, BAT7104 is expected to avoid RBC depletion and block CD47 on CD47+/PD-L1+ tumors in a more selective and tumor-enriched manner. BAT7104 was shown to effectively inhibit both pathways in vitro and demonstrated synergistic activity in inducing complete tumor regression in vivo. In non-human primates (NHP) study, BAT7104 was well tolerated with no adverse effects, suggesting a favorable therapeutic index in future clinical development. "BAT7104 has demonstrated higher anti-tumor activity with better safety profile in preclinical studies". Commented Dr. Shengfeng Li, CEO, Bio-Thera Solutions. "As the first bispecific antibody of Bio-Thera, we are pleased to see BAT7104 enter clinical development in Australia, and we will continue bringing more innovative anti-tumor drugs to cancer patients." Dr. Shengfeng Li continued.

The Phase 1, multi-center, open-label, dose-escalation clinical trial of BAT7104 is designed to assess the safety and tolerability of BAT7104. Key objectives of the study are to determine the maximum tolerated dose and recommended Phase 2 dose (RP2D), and to evaluate pharmacokinetics and preliminary efficacy in patients with advanced solid tumor. Another early stage Phase 1 clinical study evaluating BAT7104 is being conducted in China in patients with solid tumors and lymphoma. In addition, Bio-Thera Solutions is developing several additional innovative oncology assets directed at important IO targets, including PD-1, OX40, CTLA-4, and TIGIT, all in early stage clinical studies.

Repare Therapeutics to Participate at the 2022 Guggenheim Synthetic Lethality Day

On May 9, 2022 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported that members of its senior management team will participate in a fireside chat at the virtual 2022 Guggenheim Synthetic Lethality Day on Monday, May 16, 2022 at 9:00 a.m. Eastern Time (Press release, Repare Therapeutics, MAY 9, 2022, View Source [SID1234613959]).

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A live webcast of the fireside can be accessed in the Investor section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days.