On August 3, 2022 Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology company focusing on the development of T-cell-based cancer therapies, reported its Half-Year Report 2022 with an overview on its business performance and financial results (Press release, MediGene, AUG 3, 2022, View Source [SID1234617402]). The full version of the report can be downloaded here: View Source

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Business review Q2 2022 and outlook

MDG1011 – Clinically validated T cell receptor-modified T cell (TCR-T) therapy in blood cancers

In June 2021, the last patient was enrolled in the third dose cohort of the Phase I part of the Phase I/II trial of MDG1011 in blood cancer patients and Medigene successfully reported on safety, tolerability and feasibility in December 2021. In February 2022, the first positive efficacy and immune monitoring data were published. The last trial visit of a patient whose myelodysplastic syndrome did not progress to secondary acute myeloid leukemia took place in June 2022, final data are currently being analyzed and will be published upon completion.

Development partnerships

At the end of June 2022, the research term for the partnership with 2seventy bio, Inc. was successfully concluded in accordance with the contract and Medigene remains eligible for potential milestone payments and royalties on future products based on Medigene’s technology. Roivant Sciences divested its holding in Cytovant Sciences in July 2022, which subsequently became Hongsheng Sciences HK Limited (Hongsheng Sciences). Due to financing constraints, Hongsheng Sciences has temporarily suspended its development activities within the Medigene partnership, but Medigene has meanwhile already started the extensive work under the new partnership with BioNTech SE (BioNTech) signed in February 2022.

Discovery of novel T cell receptors (TCRs) against undisclosed target molecules in solid tumors

Using Medigene’s proprietary TCR screening and discovery platform, the Company continuously evaluates novel target molecules in the solid tumor arena including tumor-specific molecules of the cancer-testis-antigen family, "dark matter" antigens stemming from non-coding regions of the DNA, and as yet undisclosed targets. If these targets fulfil Medigene’s target safety criteria during screening, candidates are selected for further TCR development, as part of the Company’s ongoing process to expand its pipeline.

Changes in the Executive Management Board

Dr. Selwyn Ho joined Medigene as Chief Executive Officer (CEO) on 25 July 2022. As a consequence, Prof. Dolores Schendel stepped down as CEO at the end of 24 July 2022 and now fully focuses on her responsibilities as Chief Scientific Officer (CSO) and Head of Research and Development at Medigene.

Prof. Dolores Schendel, CSO at Medigene: "The first half of 2022 was a period of significant transition at Medigene. Importantly, we completed two central projects that have involved intense efforts over the last few years. The Phase I part of our MDG1011 TCR-T trial in blood cancer was concluded with the end-of-trial visit of the last patient at 12 months. The experience we gained here regarding high fidelity manufacturing, drug product characterization, and implementation of immune monitoring strategies for patient assessment now enables straightforward transition to development activities for TCR-Ts in solid cancer.

Secondly, the TCR discovery phase of the 2seventy bio alliance concluded at the end of June, enabling Medigene to rapidly transition to our new multi-faceted alliance with BioNTech that extends beyond projects in TCR discovery to include innovation tools designed and developed at Medigene for next generation TCR-T immunotherapies.

We are also delighted to welcome Dr. Selwyn Ho as CEO of Medigene, which means I return to focusing full time on my role as CSO and Head of Research and Development. Selwyn has the ideal experience to take over and lead Medigene at this exciting time, enabling Medigene to optimally position itself for clinical development of TCR-T immunotherapies for solid cancer in the near future."

Dr. Selwyn Ho, CEO at Medigene: "Medigene is one of the pioneers in the TCR-T space, and the strength and potential of its validated and integrated discovery platform is what attracted me to join. From TCR screening and discovery of novel targets, with the ability to further enhance the activity of our selected TCR with product optimization tools, and finally to a validated manufacturing and clinical biomarker monitoring platform, Medigene has the capabilities to develop potentially highly differentiated TCR-based therapies for solid tumors with high unmet need.

We remain focused on our partnering activities as well as advancing our pipeline of wholly owned TCRs and optimization tools for solid tumors into the clinic as soon as possible. I look forward to be able to announce and discuss our updated plans in further detail by the end of this year."

Financial development and financial forecast

The Company’s revenues increased to €25.3 m in the first half of 2022 (6M 2020: €4.3 m) mainly resulting from the new partnership with BioNTech, research and development (R&D) expenses decreased by 42% to €3.7 m (6M 2021: €6.3 m) and the EBITDA improved to €15.4 m (6M 2021: €-4.5 m) due to the partnership with BioNTech.

Management confirms the financial forecast and still expects revenues of €23-28 m, R&D expenses of €11-15 m and EBITDA of €3-5 m in 2022, without the COVID-19 pandemic or Ukraine crisis having a material impact on these expectations. These estimates do not include potential future milestone payments from existing or future partnerships or transactions, as the occurrence of such events or their timing and scope depends to a large extent on external parties and therefore cannot be reliably forecast by Medigene.

As of 30 June 2022, cash and cash equivalents and time deposits amounted to €39.4 m (31 December 2021: €22.4 m). Based on its current planning, the Company has sufficient financial resources to fund business operations into the fourth quarter of 2024.

Investor and analyst conference call

Date: Wednesday, 3 August 2022, 3:00 pm CEST (9:00 am EDT)
Registration: View Source;linkSecurityString=9253bcaa2
Speakers*: Prof. Dr. Dolores Schendel, CSO and Head of Research and Development
Dr. Birger Kohlert, CFO
*Please note: Since both the report and the presentation mainly refer to the first six months of 2022, Prof. Dr. Dolores Schendel will lead the presentation.

Please register beforehand and latest 2 hours prior to the event through the registration link provided above to receive your personal access information (phone number, passcode, personal PIN). Please don’t distribute your dial-in details which will be personalized. Please dial in at least 10 minutes before start time.

On August 3, 2022 AngioDynamics, Inc. (NASDAQ: ANGO), a leading and transformative medical technology company focused on restoring healthy blood flow in the body’s vascular system, expanding cancer treatment options, and improving quality of life for patients, reported that Stephen Trowbridge, Executive Vice President and Chief Financial Officer, will present at the Canaccord Genuity 42nd Annual Growth Conference at 2:00 p.m. ET on Wednesday, August 10, 2022 (Press release, AngioDynamics, AUG 3, 2022, View Source [SID1234617422]).

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A live webcast of the presentation will be accessible through the "Investors" section of the Company’s website at www.angiodynamics.com and will be available for replay following the event.

On August 3, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that financial results for the second quarter of 2022 and provided a business update (Press release, Regeneron, AUG 3, 2022, View Source [SID1234617340]).

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"The second quarter of 2022 was distinguished by record net product sales of EYLEA, Dupixent, and Libtayo, as well as multiple regulatory achievements for Dupixent, including U.S. approvals for atopic dermatitis among very young patients and for eosinophilic esophagitis in adults and adolescents, as well as European approval for pediatric asthma," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "In addition, we have continued to strengthen our oncology franchise, including through the purchase of worldwide rights to Libtayo as well as encouraging but preliminary anti-tumor activity observed at higher doses of our novel PSMAxCD28 costimulatory bispecific in combination with Libtayo for advanced metastatic castration-resistant prostate cancer."

Financial Highlights

"We are pleased with our second quarter 2022 financial performance, including 20% revenue growth when excluding contributions from REGEN-COV. This demonstrates the continued strength of our core business," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "Additionally, we updated our full-year 2022 financial guidance primarily to reflect the recently completed acquisition of Libtayo global rights from Sanofi, a transaction that we believe will deliver significant shareholder value over time. In the second half of 2022, we look forward to advancing our pipeline with important clinical data readouts in oncology and ophthalmology as well as continued commercial execution and prudent capital allocation to drive value creation for shareholders."

Business Highlights

Key Pipeline Progress
Regeneron has approximately 35 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

Dupixent (dupilumab)

In June 2022, the U.S. Food and Drug Administration (FDA) approved Dupixent as the first biologic medicine for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis.
In May 2022, the FDA approved Dupixent for adults and adolescents aged 12 years and older with eosinophilic esophagitis (EoE).
In April 2022, the European Commission (EC) approved Dupixent for the treatment of severe asthma in children aged 6 to 11 years.
The Company and Sanofi announced positive results from a Phase 3 trial in children aged 1 to 11 years with EoE. The trial met its primary endpoint of histological disease remission at 16 weeks with both higher and lower dose weight-tiered regimens.
The FDA accepted for priority review the supplemental Biologics License Application (sBLA) for Dupixent for adults with prurigo nodularis, with a target action date of September 30, 2022. Regulatory applications have also been submitted in the European Union (EU) and Japan.
EYLEA (aflibercept) Injection

The FDA accepted for review the sBLA for EYLEA for an every-16-weeks dosing regimen in patients with diabetic retinopathy (DR), with a target action date of February 28, 2023.
REGN5678, a PSMAxCD28 costimulatory bispecific antibody

Reported preliminary, first-in-human data in combination with Libtayo in patients with advanced metastatic castration-resistant prostate cancer.
Antibodies to SARS-CoV-2 virus

The Company is continuing to progress investigational "next generation" antibodies that are active against multiple variants including those of Omicron-lineage.
REGN5381, an agonist antibody to NPR1

A Phase 2 study in heart failure was initiated.
Corporate and Business Development Updates

In May 2022, the Company completed its acquisition of Checkmate Pharmaceuticals, Inc. for a total equity value of approximately $250 million. In connection with the acquisition, the Company obtained the rights to vidutolimod (immune activator targeting TLR9), which is in clinical development for oncology.
Effective July 1, 2022, the Company obtained the exclusive right to develop, commercialize, and manufacture Libtayo worldwide under an Amended and Restated Immuno-oncology License and Collaboration Agreement with Sanofi. Under the terms of the agreement, the Company made a $900 million up-front payment, and Sanofi is eligible to receive a $100 million regulatory milestone and up to an aggregate of $100 million in sales-based milestones upon achieving certain amounts of worldwide net product sales of Libtayo through 2023. The Company will also pay Sanofi a royalty on net product sales of Libtayo.
Also effective July 1, 2022, the Company will increase from 10% to 20% the share of its profits that are paid to Sanofi in connection with the development balance reimbursement under the antibody collaboration.
Second Quarter 2022 Financial Results

* Percentage not meaningful

** Effective July 1, 2022, the Company will record global net product sales of Libtayo.

Total revenues decreased by 44% to $2.857 billion in the second quarter of 2022, compared to $5.139 billion in the second quarter of 2021. Total revenues excluding REGEN-COV and Ronapreve(b) revenues for both periods increased by 20% to $2.849 billion in the second quarter of 2022, compared to the second quarter of 2021(a). There have been no sales of REGEN-COV in the United States during 2022 as the Company had completed its final deliveries of drug product under its agreements with the U.S. government as of December 31, 2021.

Sanofi collaboration revenue increased by 55% to $678 million in the second quarter of 2022, compared to the second quarter of 2021. This increase was primarily due to the Company’s share of profits from commercialization of antibodies, which were $497 million in the second quarter of 2022, compared to $328 million in the second quarter of 2021. The change in the Company’s share of profits from commercialization of antibodies was driven by higher Dupixent profits. Roche collaboration revenue decreased in the second quarter of 2022, compared to the second quarter of 2021, due to lower sales of Ronapreve.

Refer to Table 4 for a summary of collaboration revenue.

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded.

** Beginning with the first quarter of 2022, the Company added this new line item to its Statements of Operations, which includes IPR&D acquired in connection with asset acquisitions as well as up-front/opt-in payments related to license and collaboration agreements. Amounts recorded in this line would have historically been recorded to R&D. This change does not affect previously reported non-GAAP results for the three and six months ended June 30, 2021 as the Company recorded no such charges during either of these periods.

GAAP and non-GAAP R&D expenses increased in the second quarter of 2022, compared to the second quarter of 2021, primarily due to higher headcount and headcount-related costs and an increase in clinical manufacturing activities, partly offset by lower costs incurred in connection with REGEN-COV development activities.
Acquired IPR&D in the second quarter of 2022 included a $195 million charge related to the Company’s acquisition of Checkmate Pharmaceuticals.
The increase in GAAP and non-GAAP SG&A expenses in the second quarter of 2022, compared to the second quarter of 2021, was primarily due to higher headcount and headcount-related costs and an increase in commercialization-related expenses for EYLEA, partly offset by costs in 2021 for educational campaigns related to COVID-19 that did not recur in 2022.
GAAP and non-GAAP COGS decreased in the second quarter of 2022, compared to the second quarter of 2021, primarily due to the Company not recognizing any REGEN-COV net product sales in the United States during 2022.
Other Financial Information

GAAP other income (expense) included the recognition of net unrealized losses on equity securities of $164 million in the second quarter of 2022, compared to $409 million of net unrealized gains in the second quarter of 2021.

In the second quarter of 2022, the Company’s GAAP effective tax rate (ETR) was 11.5%, compared to 17.4% in the second quarter of 2021. The decrease in the GAAP ETR was primarily driven by the proportion of income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate, the impact of income earned in the United States during 2021 related to REGEN-COV, and, to a lesser extent, stock-based compensation. In the second quarter of 2022, the non-GAAP ETR was 13.6%, compared to 17.0% in the second quarter of 2021.

GAAP net income per diluted share was $7.47 in the second quarter of 2022, compared to $27.97 in the second quarter of 2021. Non-GAAP net income per diluted share was $9.77 in the second quarter of 2022, compared to $25.80 in the second quarter of 2021. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

During the second quarter of 2022, the Company repurchased shares of common stock under its share repurchase program, and recorded the cost of the shares received, or $394 million, as Treasury Stock. As of June 30, 2022, $2.099 billion remained available for share repurchases under the program.

2022 Financial Guidance(d)

The Company’s full year 2022 financial guidance consists of the following components (inclusive of updates made in connection with the Company’s purchase of Sanofi’s stake in Libtayo and acquisition of Checkmate Pharmaceuticals):

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been or are expected to be recorded.

** ETR guidance excludes the impact of the provision requiring capitalization and amortization of R&D expenses enacted as part of the Tax Cuts and Job Act (TCJA), as management’s current expectation is it will be deferred or repealed by Congress in 2022. If this provision of the TCJA is not deferred or repealed, the Company would expect its ETR to be lower than the guidance disclosed herein.

A reconciliation of full year 2022 GAAP to non-GAAP financial guidance is included below:

This press release uses non-GAAP R&D, non-GAAP SG&A, non-GAAP COGS, non-GAAP gross margin on net product sales, non-GAAP other income (expense), net, non-GAAP ETR, non-GAAP net income, non-GAAP net income per share, total revenues excluding REGEN-COV and Ronapreve, and free cash flow, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles (GAAP). These non-GAAP financial measures are computed by excluding certain non-cash and/or other items from the related GAAP financial measure. The Company also includes a non-GAAP adjustment for the estimated income tax effect of reconciling items. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company’s control (such as the Company’s stock price on the dates share-based grants are issued or changes in the fair value of the Company’s investments in equity securities) or items that are not associated with normal, recurring operations (such as restructuring- or integration-related expenses). Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. With respect to free cash flows, the Company believes that this non-GAAP measure provides a further measure of the Company’s operations’ ability to generate cash flows. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company’s core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company’s non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by Regeneron should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP.

The casirivimab and imdevimab antibody cocktail is known as REGEN-COV in the United States and Ronapreve in other countries. The Company records net product sales of REGEN-COV in the United States and Roche records net product sales of Ronapreve outside the United States.

The Company’s collaborators provide it with estimates of the collaborators’ respective sales and the Company’s share of the profits or losses (if applicable) from commercialization of products for the most recent fiscal quarter. These estimates are revised, if necessary, in subsequent periods if the Company’s actual share of the profits or losses differ from those estimates.

The Company’s 2022 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release.

Gross margin on net product sales represents gross profit expressed as a percentage of total net product sales recorded by the Company. Gross profit is calculated as net product sales less cost of goods sold.

Corresponding reimbursements from collaborators and others for manufacturing of commercial supplies is recorded within revenues.

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its second quarter 2022 financial and operating results on Wednesday, August 3, 2022, at 8:30 AM Eastern Time. Participants may access the conference call live via webcast, or register in advance and participate via telephone, on the "Investors and Media" page of Regeneron’s website at View Source Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

On August 3, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported business highlights and financial results for the second quarter ended June 30, 2022 (Press release, Fate Therapeutics, AUG 3, 2022, View Source [SID1234617370]).

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"We continue to make important strides across our clinical, regulatory, and manufacturing operations to support pivotal readiness of our iPSC-derived NK cell product candidates for B-cell lymphoma, and are looking forward to meeting with the FDA in the third quarter to discuss registrational pathways for the treatment of relapsed / refractory aggressive lymphomas, including for patients that have previously failed CD19-targeted CAR T-cell therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We are also excited that clinical investigation of FT536 has initiated to assess the targeting of oncogenic and cellular stress ligands, a novel pan-tumor-targeting strategy with the potential to overcome common mechanisms of tumor escape that frequently emerge in patients with advanced solid tumors. Finally, we continue to drive our collaborations with Janssen and Ono with strong momentum, and are well positioned to achieve significant milestones and advance three multiplexed-engineered, CAR-targeted cell collaboration candidates into clinical development over the next 12 months."

B-cell Malignancy Disease Franchise

FT596+R Enrollment Ongoing in Single- and Multi-dose, Multi-cycle Cohorts for R/R BCL. The Company’s multicenter Phase 1 study of FT596 in combination with rituximab (FT596+R) for relapsed / refractory (r/r) B-cell lymphoma (BCL) is currently enrolling patients in single- and two-dose cohorts at up to 1.8 billion cells per dose. Each cohort permits eligible patients to receive multiple treatment cycles. Upon further clearance of dose-limiting toxicities (DLTs), the clinical protocol permits additional assessment of dose and schedule, including the opening of three-dose cohorts as well as continued dose escalation and expansion.
Study Start-up Initiated for FT596+R-CHOP in First-line Aggressive B-cell Lymphoma. The Company has submitted a new clinical protocol to the FT596 Investigational New Drug (IND) application and has initiated study start-up to assess the safety and activity of adding FT596 to R-CHOP, the standard first-line immunochemotherapy for patients with aggressive lymphomas. The proposed treatment schema includes administering up to six doses of FT596, with each dose being administered with each of six standard cycles of R-CHOP. The objective of the Phase 1 study is to inform the feasibility of developing FT596, without conditioning chemotherapy, for the treatment of patients with newly-diagnosed aggressive BCL in the outpatient community setting.
FT516 Multi-disciplinary RMAT Meeting Schedule for 3Q22. The Company is scheduled to hold its FT516 Regenerative Medicine Advanced Therapy (RMAT) Type B multi-disciplinary meeting with the U.S. Food and Drug Administration (FDA) in the third quarter of 2022. The meeting agenda includes discussion of registrational pathways for the treatment of patients with aggressive lymphomas, including patients who have relapsed or are refractory to FDA-approved CD19-directed chimeric antigen receptor (CAR) T-cell therapy. No standard therapies are available for these post-CAR T-cell therapy patients, and recent retrospective analyses of real-world data presented at the 2021 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) demonstrate extremely poor treatment outcomes with complete response rates of administered therapies ranging from 5% to 25% and overall survival ranging from 5.2 months to 7.5 months.
FT516+R Enrollment Ongoing in Multiple Multi-dose, Multi-cycle, Disease-specific Expansion Cohorts for R/R BCL. The Company’s multicenter Phase 1 study of FT516 in combination with rituximab (FT516+R) for r/r BCL is currently enrolling patients in multiple disease-specific, multi-dose, multi-cycle expansion cohorts at 900 million cells per dose, including patients with r/r aggressive lymphomas who have previously been treated with CD19-targeted CAR T-cell therapy.
FT819 Enrollment Ongoing in Third Single-dose and Second Multi-dose Escalation Cohorts. The Company is conducting a landmark Phase 1 study of FT819, the first-ever T-cell therapy manufactured from a clonal master induced pluripotent stem cell (iPSC) line to undergo clinical investigation. The product candidate’s clonal master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct (1XX-CAR19) integrated into the T-cell receptor alpha constant (TRAC) locus, ensuring complete bi-allelic disruption of T-cell receptor expression and promoting uniform CAR expression. Dose escalation is ongoing in the third single-dose escalation cohort of 360 million cells and in the second three-dose escalation cohort of 60 million cells per dose for r/r BCL.
Multiple Myeloma Franchise

FT576 Enrollment Ongoing in Phase 1 Study for R/R MM. The multicenter Phase 1 study is designed to assess single-dose and multi-dose treatment schedules of FT576 as monotherapy and in combination with daratumumab (FT576+D) for the treatment of r/r multiple myeloma (MM). There were no DLTs observed in the second single-dose escalation cohort (300 million cells) as monotherapy or in the first single-dose escalation cohort (100 million cells) in combination with daratumumab; and no events of any grade of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD) have been reported. Enrollment is currently ongoing in the two-dose escalation cohorts with FT576 administered on Days 1 and 15.
FT538 Enrollment Ongoing in Third Multi-dose Escalation Cohort. The Company’s Phase 1 study is designed to assess three once-weekly doses of FT538 in combination with daratumumab for the treatment of r/r MM, and is currently enrolling patients in the third multi-dose escalation cohort (1 billion cells per dose). No DLTs, and no events of any grade of CRS, ICANS, or GvHD, have been reported.
AML Disease Franchise

FT538 Enrollment Ongoing in Fourth Multi-dose Escalation Cohort. The Company’s Phase 1 study is designed to assess three once-weekly doses of FT538 as monotherapy for the treatment of r/r acute myeloid leukemia (AML), and is currently enrolling patients in the fourth multi-dose escalation cohort (1.5 billion cells per dose). In addition, an investigator-initiated study of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab, which is designed to assess the therapeutic potential of targeting CD38+ leukemic blasts, is enrolling patients in the fourth multi-dose escalation cohort (1.5 billion cells per dose).
Solid Tumor Franchise

First Patient Treated with FT536 CAR MICA/B-targeted NK Cell Product Candidate. The multicenter Phase 1 study is designed to assess a multi-dose, multi-cycle treatment schedule as monotherapy and in combination with monoclonal antibody therapy for the treatment of advanced solid tumors. FT536 uniquely targets the alpha-3 domains of the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB); a novel targeting approach designed to overcome proteolytic shedding of MICA/B by cancer cells as a means of immune cell escape. The first patient has been treated in the first three-dose escalation cohort (100 million cells per dose) as monotherapy, with FT536 administered on Days 1, 8, and 15. Upon clearance of DLTs in this first dose cohort, the clinical protocol allows combination with each of five monoclonal antibodies to promote multi-antigen targeting: EGFR- and MET-targeted amivantamab; EGFR-targeted cetuximab; HER2-targeted trastuzumab; PD1-targeted pembrolizumab; and PDL1-targeted avelumab. Eligible patients may receive up to two FT536 treatment cycles, and additional FT536 treatment cycles may be administered to patients who achieve initial clinical response.
iPSC-derived CAR T-cell with Seven Functional Modalities for Solid Tumors Featured at ASGCT (Free ASGCT Whitepaper). At the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 25th Annual Meeting held in May, the Company unveiled the derivation of a first-of-kind, multiplexed-engineered master iPSC line incorporating seven functional elements, which was created through the integration of multiple transgenes into multiple loci at the single-cell level. CAR T cells produced from the single-cell derived, multiplexed-engineered clonal iPSC line expressed synthetic features optimized for recognizing, binding, and killing solid tumors, and showed improved anti-tumor activity in vitro, including resistance to a key component of the tumor-suppressive microenvironment TGF-beta.
Expanded Collaboration with ONO to Add Second Solid Tumor Antigen Program. In the second quarter, the Company expanded its off-the-shelf, iPSC-derived, cell-based cancer immunotherapy collaboration with Ono Pharmaceutical Co., Ltd. (ONO) to add a second solid tumor antigen program as well as include the development of both CAR NK and CAR T-cell candidates. Under the original agreement entered into between the Company and ONO in September 2018, ONO has contributed novel binding domains targeting an initial solid tumor antigen, and the Company is currently conducting preclinical development of a multiplexed-engineered, iPSC-derived CAR T-cell product candidate. Upon achievement of a pre-defined preclinical milestone, ONO has an option to assume responsibility for worldwide development and commercialization, with the Company retaining joint development and commercialization rights in the United States and Europe.
Janssen Collaboration Highlights

Clinical Development Option Exercised for First Antigen Program. In May, Janssen exercised its commercial option for an iPSC-derived CAR NK cell collaboration product targeting an antigen expressed on certain hematologic malignancies, triggering a milestone payment to the Company. The Company expects to submit its first IND application under the collaboration during the second half of 2022. Pursuant to its commercial option exercise, Janssen has an exclusive license for development and commercialization of the product candidate, and the Company is eligible to receive clinical, regulatory, and commercial milestones, plus double-digit royalties on worldwide commercial sales of the product candidate. In addition, the Company retains the right to elect to co-commercialize, and share equally in profits and losses, in the United States, subject to its payment of certain clinical development costs and adjustments in milestone and royalty payments.
Preclinical Development Ongoing for Two Additional Antigen Programs. The Company and Janssen are also conducting preclinical development of a second iPSC-derived, CAR-targeted cell candidate for an antigen expressed on certain hematologic malignancies and a third iPSC-derived, CAR-targeted cell candidate for an antigen expressed on solid tumors. In addition, during the second quarter, Janssen selected a solid tumor-associated antigen as its fourth and final program for initiation of candidate development.
Second Quarter 2022 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of June 30, 2022 were $580.8 million.
Total Revenue: Revenue was $18.5 million for the second quarter of 2022, which was derived from the Company’s collaborations with Janssen and ONO.
R&D Expenses: Research and development expenses were $81.3 million for the second quarter of 2022, which includes $13.6 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $20.4 million for the second quarter of 2022, which includes $7.0 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 96.9 million, and preferred shares outstanding were 2.8 million, as of June 30, 2022. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Wednesday, August 3, 2022 at 5:00 p.m. ET to review financial and operating results for the quarter ended June 30, 2022. In order to participate in the conference call, please dial (877) 545-0320 (domestic) or (973) 528-0002 (international) and refer to conference ID 687045. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of therapeutic antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of relapsed / refractory acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of relapsed / refractory B-cell lymphoma (NCT04023071).

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity and prevents antigen escape, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636). FT538 is also being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05069935).

About FT576
FT576 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).

About FT536
FT536 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that uniquely targets the alpha-3 domains of the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB); a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. High expression of MICA and MICB proteins (MICA/B), which is induced by cellular stress, damage or transformation, has been reported on many solid tumors, and while cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can recognize and bind the membrane-distal alpha-1 and alpha-2 domains of MICA/B, cancer cells frequently evade immune cell recognition by proteolytic shedding of the alpha-1 and alpha-2 domains of MICA/B. Recent publications have demonstrated that antibody targeting of the MICA/B alpha-3 domains specifically prevents MICA/B shedding and restores NK cell-mediated immunity (DOI:10.1126/science.aao0505), and that cancers with B2M and JAK1 inactivating mutations resulting in loss of MHC Class I expression can be effectively targeted with MICA/B alpha-3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors resistant to cytotoxic T cells (DOI: 10.1158/2326-6066.CIR-19-0483). In preclinical studies, FT536 has been shown to elicit innate cytotoxicity, MICA/B-specific activity against multiple solid tumor targets, and antibody cellular cytotoxicity (ADCC) in combination with tumor-targeting antibodies. FT536 is being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05395052).

On August 3, 2022 Pacira BioSciences, Inc. (Nasdaq: PCRX), the industry leader in its commitment to non-opioid pain management and regenerative health solutions, reported financial results for the second quarter of 2022 (Press release, Pacira Pharmaceuticals, AUG 3, 2022, View Source;991.htm [SID1234617386]).

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Second Quarter 2022 Financial Highlights

Total revenues of $169.4 million
Net product sales of $137.0 million for EXPAREL, $27.4 million for ZILRETTA, and $3.2 million for iovera°
Net income of $19.9 million, or $0.44 per share (basic) and $0.40 per share (diluted)
Adjusted EBITDA of $44.9 million
"We achieved record revenue for the second quarter, which was marked by strength across the entire portfolio amid ongoing market headwinds. We continue to invest in our training facilities and marketing programs to help facilitate growth throughout the balance of the year and beyond," said Dave Stack, chairman and chief executive officer of Pacira BioSciences. "The second quarter also marked our 21st consecutive quarter of positive adjusted EBITDA, which underscores our consistency and reliability as stewards for our stakeholders. We continue to execute our strategy, confident that the ongoing transition of surgeries to the outpatient setting and other market dynamics will support our growth as we work to create lasting value."

Recent Business Highlights

Completion of Patient Enrollment in Two Phase 3 Registration Studies of EXPAREL as a Lower Extremity Nerve Block. Today the company is announcing the completion of patient enrollment in its two Phase 3 studies of EXPAREL as a nerve block in lower extremity surgeries. The first study is evaluating EXPAREL as an adductor canal block for total knee arthroplasty and the second is evaluating EXPAREL as a popliteal sciatic nerve block for bunionectomy. The company believes positive results from these studies will form the basis for a Supplemental New Drug Application submission seeking label expansion to include lower extremity nerve blocks.
New EXPAREL Patent and Notice of Allowance. In June 2022, the U.S. Patent and Trademark Office (USPTO) issued Patent Number 11,357,727. This patent is a product by process patent, with an expiration date of January 22, 2041. This patent is now listed in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalents Evaluations (Orange Book). In July, the company received a Notice of Allowance from the USPTO for a U.S. Patent Application claiming chemical composition of EXPAREL. After issuance, Pacira will submit this patent for listing in the Orange Book.
Second Quarter 2022 Financial Results

Total revenues were $169.4 million in the second quarter of 2022, versus the $135.6 million reported for the second quarter of 2021.
EXPAREL net product sales were $137.0 million in the second quarter of 2022, versus the $130.1 million reported for the second quarter of 2021.
ZILRETTA net product sales were $27.4 million in the second quarter of 2022. The company began recognizing ZILRETTA sales upon completing its acquisition of Flexion Therapeutics, Inc. in November 2021.
Second quarter 2022 iovera° net product sales were $3.2 million, versus the $3.8 million reported for the second quarter of 2021.
Sales of bupivacaine liposome injectable suspension to a third-party licensee for use in veterinary practice were $1.0 million in the second quarter of 2022, versus the $1.0 million reported for the second quarter of 2021.
Second quarter 2022 royalty and collaborative licensing and milestone revenues were $0.8 million, versus the $0.7 million reported for the second quarter of 2021.
Total operating expenses were $138.2 million in the second quarter of 2022, versus the $100.7 million reported for the second quarter of 2021.
Research and development (R&D) expenses were $26.3 million in the second quarter of 2022, compared to $12.6 million in the second quarter of 2021. R&D expenses included $5.1 million and $4.6 million of product development and manufacturing capacity expansion costs in the second quarters of 2022 and 2021, respectively.
Selling, general and administrative (SG&A) expenses were $65.0 million in the second quarter of 2022, compared to $50.8 million in the second quarter of 2021.
GAAP net income was $19.9 million, or $0.44 per share (basic) and $0.40 per share (diluted), in the second quarter of 2022, compared to $19.1 million, or $0.43 per share (basic) and $0.42 per share (diluted), in the second quarter of 2021.
Non-GAAP net income was $24.0 million, or $0.53 per share (basic) and $0.51 per share (diluted), in the second quarter of 2022, compared to $35.3 million, or $0.80 per share (basic) and $0.77 per share (diluted), in the second quarter of 2021.
Adjusted EBITDA was $44.9 million in the second quarter of 2022, compared to $50.3 million in the second quarter of 2021.
Pacira ended the second quarter of 2022 with cash, cash equivalents and short-term available-for-sale investments ("cash") of $316.4 million. Cash provided by operations was $29.8 million in the second quarter of 2022, compared to $30.1 million in the second quarter of 2021.
Pacira had 45.5 million basic and 52.5 million diluted weighted average shares of common stock outstanding in the second quarter of 2022.
See "Non-GAAP Financial Information" below.

Financial Guidance

Since early 2020, the company’s revenues have been impacted by COVID-19 and pandemic-related challenges that included the significant postponement or suspension in the scheduling of elective surgical procedures due to public health guidance and government directives. While the degree of impact has diminished during the course of the pandemic due to the introduction of vaccines and the lessening of elective surgery restrictions, certain pandemic-related operational challenges persist. It remains unclear how long it will take the elective surgery market to normalize or if restrictions on elective procedures will recur due to future COVID-19 variants or otherwise. Given the continued uncertainty around labor shortages, COVID-19 and the pace of recovery for the elective surgery market, the company is currently not providing revenue or gross margin guidance. To provide greater transparency, Pacira is reporting monthly intra-quarter unaudited net product sales for EXPAREL, ZILRETTA, and iovera° until it has gained enough visibility around the impacts of COVID-19. Pacira is also providing weekly EXPAREL utilization and elective surgery data within its investor presentation, which is accessible at investor.pacira.com

Today the company is reiterating its full-year 2022 operating expense guidance as follows:

Non-GAAP R&D expense of $75 million to $85 million; and
Non-GAAP SG&A expense of $220 million to $230 million.
The company is adjusting its full-year 2022 guidance for stock-based compensation to $47 million to $50 million.

See "Non-GAAP Financial Information" below.

Today’s Conference Call and Webcast Reminder

The Pacira management team will host a conference call to discuss the company’s financial results and recent developments today, Wednesday, August 3, 2022, at 8:30 a.m. ET. To participate in the conference call, dial 1-800-715-9871 and provide the passcode 9287305. International callers may dial 1-646-307-1963 and use the same passcode. In addition, a live audio of the conference call will be available as a webcast. Interested parties can access the event through the "Events" page on the Pacira website at investor.pacira.com.

For those unable to participate in the live call, a replay will be available at 1-800-770-2030 (domestic) or 1-609-800-9909 (international) using the passcode 9287305. The replay of the call will be available for one week from the date of the live call. The webcast will be available on the Pacira website for approximately two weeks following the call.

Non-GAAP Financial Information

This press release contains financial measures that do not comply with U.S. generally accepted accounting principles (GAAP), such as non-GAAP net income, non-GAAP net income per common share, non-GAAP weighted average common shares outstanding-diluted, non-GAAP cost of goods sold, non-GAAP research and development (R&D) expense, non-GAAP selling, general and administrative (SG&A) expense, and adjusted EBITDA (as defined below), because these non-GAAP financial measures exclude the impact of items that management believes affect comparability or underlying business trends.

These measures supplement the company’s financial results prepared in accordance with GAAP. Pacira management uses these measures to better analyze its financial results, estimate its future cost of goods sold, R&D expense and SG&A expense outlook for 2022 and to help make managerial decisions. In management’s opinion, these non-GAAP measures are useful to investors and other users of the Company’s financial statements by providing greater transparency into the operating performance of Pacira and its future outlook. Such measures should not be deemed to be an alternative to GAAP requirements or a measure of liquidity for Pacira. Non-GAAP measures are also unlikely to be comparable with non-GAAP disclosures released by other companies. See the tables below for a reconciliation of GAAP to non-GAAP measures.