On November 9, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported the publication of abstracts with clinical data for Iovance tumor-infiltrating lymphocyte (TIL) therapy in combination with pembrolizumab in patients with advanced cancers and for Iovance TIL cell therapy in relapsed, refractory lung cancer (Press release, Iovance Biotherapeutics, NOV 9, 2021, View Source [SID1234594874]). Additional updates will be provided at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting from November 12-14, 2021 in Washington, D.C. and virtually.

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Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "Our latest clinical data in the SITC (Free SITC Whitepaper) abstracts further support the power of our TIL platform and our ongoing TIL development across multiple solid-tumor cancers and various treatment settings. We look forward to highlighting clinical data that suggest TIL in combination with pembrolizumab may increase response rates as an early line treatment for advanced cervical cancer, melanoma, and head and neck cancer. SITC (Free SITC Whitepaper) will also be our first medical meeting to present clinical results for Iovance TIL in heavily pre-treated patients with metastatic non-small cell lung cancer."

Lifileucel in Combination with Pembrolizumab in Advanced Cancers
Early-line treatment with single-agent pembrolizumab achieved an overall response rate (ORR) of 33% in patients with advanced melanoma¹ and 17% in patients with head and neck squamous cell carcinoma (HNSCC).² Novel early-line combination therapies are needed to improve rate and depth of responses with manageable long-term safety. Clinical data in the SITC (Free SITC Whitepaper) abstract show encouraging response rates after lifileucel plus pembrolizumab in patients with immune checkpoint inhibitor (ICI)-naïve advanced melanoma and HNSCC from the IOV-COM-202 study as well as patients from the C-145-04 clinical study who were ICI- and chemotherapy-naive. The ORR in all cohorts was assessed by investigator using RECIST 1.1 and listed in the abstract as follows (July 9, 2021 data cutoff):

Cervical cancer (Cohort 3 in C-145-04 cervical cancer study): ORR was 50.0% with five out of 10 patients who had a confirmed objective response, including one complete response (CR), four partial responses (PR), and four best responses of stable disease (SD).
Metastatic melanoma (Cohort 1A in IOV-COM-202 study): ORR was 87.5% with seven out of eight patients who had a confirmed objective response, including three CRs, three PRs, one unconfirmed PR (uPR), and one best response of SD.
HNSCC (Cohort 2A in IOV-COM-202 study): ORR was 42.9% with six out of 14 patients who had a confirmed objective response, including one CR, one unconfirmed CR (uCR), four PRs, and seven best responses of SD.
The treatment-emergent adverse event (TEAE) profile across all cohorts was consistent with the underlying disease and known adverse event (AE) profiles of pembrolizumab, nonmyeloablative lymphodepletion (NMA-LD), and IL-2. Additional and updated results for TIL plus pembrolizumab in cervical, melanoma and HNSCC will be available in an oral presentation at SITC (Free SITC Whitepaper).

LN-145 in Relapsed/Refractory Metastatic Non-Small Cell Lung Cancer (mNSCLC)
Clinical data in the abstract for Iovance TIL therapy LN-145 in relapsed/refractory mNSCLC demonstrated responses in heavily pretreated patients with NSCLC, regardless of PD-L1 expression, and warrant further investigation of LN-145 as a single-agent and in combination in patients with NSCLC in ongoing Iovance clinical studies IOV-LUN-202 and IOV-COM-202.

Consistent with previously announced results, the ORR was 21.4% in the full analysis set (n=28) and 25% in the efficacy-evaluable set (n=24) from the fully enrolled Cohort 3B of the ongoing basket study IOV-COM-202 (June 24, 2021 cutoff). Confirmed responses included one complete metabolic response and five PRs, including two responders with PD-L1 negative tumors. TIL was most commonly harvested from lung metastases (57.1%). All patients had progressed on prior ICI therapy, including patients with oncogene-driven tumors. The TEAE profile was consistent with the underlying NSCLC and known adverse event profiles of NMA-LD and IL-2. Additional and updated data from Cohort 3B will be available in a poster at the SITC (Free SITC Whitepaper) Annual Meeting.

Iovance Posters and Presentations at SITC (Free SITC Whitepaper) Annual Meeting (November 12-14, 2021)

Title: Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancers
Authors: D O’Malley, et al.
Presentation Type: Oral Presentation
Date and Time: Saturday, November 13, 2021 at 4:30 p.m. ET
Abstract ID: 492

Title: First phase 2 results of autologous tumor-infiltrating lymphocyte (TIL; LN-145) monotherapy in patients with advanced, immune checkpoint inhibitor-treated, non-small cell lung cancer (NSCLC)
Authors: A Schoenfeld, et al.
Presentation Type: Poster (available online beginning on Friday, November 12, 2021 at 7 a.m. ET)
Abstract ID: 458

Title: Successful generation of tumor-infiltrating lymphocyte (TIL) product from renal cell carcinoma (RCC) tumors for adoptive cell therapy
Authors: B Halbert, et al.
Presentation Type: Poster (available online beginning on Friday, November 12, 2021 at 7 a.m. ET)
Abstract ID: 176

Title: Expansion of tumor-infiltrating lymphocytes (TIL) using static bag for the clinical manufacturing rapid expansion protocol (REP) process
Authors: K Onimus, et al.
Presentation Type: Poster (available online beginning on Friday, November 12, 2021 at 7 a.m. ET)
Abstract ID: 101

Conference Call and Webcast on Saturday, November 13, 2021 at 5:30pm ET
Iovance will host a webcast and conference call on Saturday, November 13, at 5:30 p.m. ET to discuss SITC (Free SITC Whitepaper) clinical data updates for Iovance TIL cell therapy in relapsed, refractory lung cancer as well as Iovance TIL in combination with pembrolizumab in patients with advanced cancers.

Iovance senior leadership will be joined by the following key opinion leaders and principal investigators in Iovance clinical studies:

Omid Hamid, MD, Chief of Research/ImmunoOncology, The Angeles Clinic and Research Institute; Co-Director, Cutaneous Malignancy Program, Cedars Sinai CANCER
David M. O’Malley, MD, Professor of Obstetrics and Gynecology at The Ohio State University College of Medicine; Director of the Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)
Adam J. Schoenfeld, MD, Medical Oncologist at Memorial Sloan Kettering Cancer Center
The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 3263399. The live webcast can be accessed in the Investors section of the company’s website at www.iovance.com. The archived webcast will be available for one year following the event.

On November 9, 2021 Vericel Corporation (NASDAQ:VCEL), a leader in advanced therapies for the sports medicine and severe burn care markets, reported financial results and business highlights for the third quarter ended September 30, 2021 (Press release, Vericel, NOV 9, 2021, View Source [SID1234594873]).

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Third Quarter 2021 Financial Highlights

Total net revenue of $34.5 million, compared to $32.3 million in the third quarter of 2020
MACI net revenue of $23.9 million, Epicel net revenue of $9.8 million, and NexoBrid revenue of $0.8 million related to the U.S. Biomedical Advanced Research and Development Authority (BARDA) procurement for emergency response preparedness
Gross margin of 64%, compared to 70% in the third quarter of 2020
Net loss of $4.9 million, or $0.11 per share, compared to net income of $3.6 million, or $0.08 per share, in the third quarter of 2020
Non-GAAP adjusted EBITDA of $4.3 million, compared to $6.7 million in the third quarter of 2020
Operating cash flow of $3.6 million
As of September 30, 2021, the Company had approximately $119 million in cash and investments, compared to approximately $100 million as of December 31, 2020, and no debt
Year-to-Date 2021 Financial Highlights

Total net revenue of $108.6 million, compared to $79.0 million in 2020
MACI net revenue of $74.2 million, Epicel net revenue of $31.8 million, and NexoBrid revenue of $2.6 million related to BARDA procurement for emergency response preparedness
Gross margin of 66%, compared to 64% for the same period in 2020
Net loss of $12.0 million, or $0.26 per share, compared to net loss of $9.4 million, or $0.21 per share, for the same period in 2020
Non-GAAP adjusted EBITDA of $16.7 million, compared to $2.5 million for the same period in 2020
Operating cash flow of $18.5 million
Business Highlights and Updates

Growth in surgeons taking MACI biopsies in 2021 is on track to exceed 20% and growth in total MACI biopsies is expected to exceed 30%, compared to 2020
Epicel net revenue growth of 48% compared to the third quarter of 2020 and the fourth straight quarter with Epicel revenue over $9 million
Growth of over 30% in Epicel biopsies and treated patients through the first nine months of 2021 compared to the same period in 2020
Following a Type A meeting with the FDA, the Company anticipates resubmission of the NexoBrid Biologics License Application in mid-2022
Expanded executive leadership team and appointed Patrick Fowler as Vericel’s Senior Vice President of Corporate Development and Strategy
"Despite additional COVID-19 disruptions in the third quarter, the Company delivered solid commercial and operational results and continued to generate top-line revenue growth, positive adjusted EBITDA and operating cash flow for the quarter," said Nick Colangelo, President and CEO of Vericel. "Based on the strength of the underlying growth drivers for MACI and Epicel, we are poised to deliver strong growth for both of our franchises this year with Epicel growth of approximately 50% for the year and with MACI expected to achieve the highest fourth quarter sequential revenue growth since launch and record quarterly revenue to close the year."

Full-Year 2021 Financial Guidance Update

Total net revenue now expected to increase 27%-30% to approximately $158-$161 million
Gross margin now expected to be approximately 70%
Adjusted EBITDA margin now expected to be approximately 22%
Estimated operating expenses of approximately $114 million
Third Quarter 2021 Results
Total net revenue for the quarter ended September 30, 2021 increased 7% to $34.5 million, compared to $32.3 million in the third quarter of 2020. Total net product revenue for the quarter included $23.9 million of MACI (autologous cultured chondrocytes on porcine collagen membrane) net revenue and $9.8 million of Epicel (cultured epidermal autografts) net revenue, compared to $24.4 million of MACI net revenue and $6.7 million of Epicel net revenue, respectively, in the third quarter of 2020. Total net revenue for the quarter also included $0.8 million of revenue related to the procurement of NexoBrid (concentrate of proteolytic enzymes enriched in bromelain) by BARDA for emergency response preparedness, compared to $1.2 million in the third quarter of 2020.

Gross profit for the quarter ended September 30, 2021 was $22.1 million, or 64% of net revenue, compared to $22.5 million, or 70% of net revenue, for the third quarter of 2020.

Total operating expenses for the quarter ended September 30, 2021 were $27.1 million, compared to $19.0 million for the same period in 2020. The increase in operating expenses was primarily due to an increase in stock-based compensation expense driven by share price appreciation and lower spend in the prior year due to COVID-19-related factors.

Net loss for the quarter ended September 30, 2021 was $4.9 million, or $0.11 per share, compared to net income of $3.6 million, or $0.08 per share, for the third quarter of 2020.

Non-GAAP adjusted EBITDA for the quarter ended September 30, 2021 was $4.3 million, or 12% of net revenue, compared to $6.7 million, or 21% of net revenue, for the third quarter of 2020. A table reconciling non-GAAP measures is included in this press release for reference.

As of September 30, 2021, the Company had approximately $119 million in cash and investments, compared to approximately $100 million as of December 31, 2020, and no debt.

Conference Call Information
Today’s conference call will be available live at 8:30am Eastern Time and can be accessed through the Investor Relations section of the Vericel website at View Source." target="_blank" title="View Source." rel="nofollow">View Source A slide presentation with highlights from today’s conference call will be available on the webcast and in the Investor Relations section of the Vericel website. Please access the site at least 15 minutes prior to the scheduled start time in order to download the required audio software, if necessary. To participate in the live call by telephone, please call (877) 312-5881 and reference Vericel Corporation’s second quarter 2021 investor conference call. If calling from outside the U.S., please use the international phone number (253) 237-1173.

If you are unable to participate in the live call, the webcast will be available at View Source until November 9, 2022. A replay of the call will also be available until 11:30am (EDT) on November 13, 2021 by calling (855) 859-2056, or from outside the U.S. by calling (404) 537-3406. The conference ID is 2998214.

On November 9, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, reported that the abstract titled, "Allogeneic CAR T cells with Deoxycytidine Kinase Knockdown Demonstrate Resistance to Fludarabine" has been accepted for poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting taking place November 10 – 14, 2021 in Washington, D.C (Press release, Precision Biosciences, NOV 9, 2021, View Source [SID1234594872]).

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Abstract/Poster Details:

Abstract Number & Title: Abstract #140. Allogeneic CAR T cells with Deoxycytidine Kinase Knockdown Demonstrate Resistance to Fludarabine
Category: Cellular Therapies
Authors: Michelle B. Pires, M.S., and Aaron J. Martin, Ph.D., both of Precision BioSciences

Abstracts for the SITC (Free SITC Whitepaper) 36th Annual Meeting are now available on the SITC (Free SITC Whitepaper) Annual Meeting website and in the Journal for ImmunoTherapy of Cancer (JITC). This abstract will be presented as an electronic poster that will be displayed on the SITC (Free SITC Whitepaper) 2021 virtual meeting platform from 7 AM EST on Friday, November 12, 2021 until the virtual meeting platform is closed on January 9, 2022.

In this preclinical study, ARCUS gene editing was used to disrupt the endogenous T cell receptor by inserting a transgene carrying a CD19-specific CAR and an RNAi sequence designed to specifically knockdown deoxycytidine kinase (dCK), a protein that converts fludarabine from its prodrug form to an active compound. This single-step approach generated allogeneic, fludarabine-resistant (FluR) CAR T cells. In these cells, the dCK RNAi sequence produced a 70% reduction in dCK mRNA abundance, and resistance to fludarabine was confirmed in vitro. Additionally, treatment of tumor-bearing mice with fludarabine and FluR CAR T cells resulted in enhanced tumor clearance and survival compared to mice receiving control CAR T cells alone or control CAR T cells and fludarabine.

On November 9, 2021 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL inhibitors for severe unmet medical needs, reported that it will deliver an e-poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place online from 10th-14th November 2021 (Press release, BerGenBio, NOV 9, 2021, View Source [SID1234594871]).

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The e-poster presentation provides pre-clinical and clinical data suggesting that bemcentinib restored response to anti-PD-1 treatments in non-small cell lung cancer (NSCLC) patients harboring STK11 mutations. STK11 is an important tumor suppressor gene reported in some studies to confer immunotherapy resistance in NSCLC. STK11 mutations are present in about 10-20% of NSCLC patients.

In pre-clinical NSCLC mouse models harboring STK11 mutations, sensitivity to PD-1 blockade was evaluated in the absence and presence of bemcentinib. Systemic inhibition of AXL with bemcentinib resulted in the expansion of tumor-associated T cells and restored therapeutic response to anti-PD-1 check point inhibition.

In parallel, data from BerGenBio’s Phase II bemcentinib and pembrolizumab combination study (BGBC008) in advanced NSCLC showed that 3 of 3 evaluable patients with identified STK11 mutations demonstrated objective clinical response / clinical benefit to the combination of bemcentinib and pembrolizumab.

Martin Olin, Chief Executive Officer at BerGenBio, commented: "While the data are limited, they suggest a mechanism by which treatment with bemcentinib could restore sensitivity to anti-PD-1 treatment in NSCLC patients harboring STK11 mutations. Up to 20% of the NSCLC patient population has been reported to harbor STK11 mutations representing a large subgroup of NSCLC."

Mutations in the tumor suppressor STK11/LKB1 have in some studies been reported as associated with negative predictive and prognostic impact in NSCLC patients receiving anti-PD-1/PD-L1 treatments. STK11 mutant tumors are characterized by a suppressive tumor micro-environment devoid of cytotoxic T cells. The study hypothesized that targeting the receptor tyrosine kinase AXL, a known driver of an innate immune suppressive microenvironment, would restore sensitivity to PD-1 blockade in pre-clinical models as well as in patients harboring STK11 mutated NSCLC.

Full abstracts are available on the SITC (Free SITC Whitepaper) website here: View Source

Full details of the presentation are below.

Title: AXL targeting with bemcentinib restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through innate immune cell mediated expansion of TCF1+ CD8 T cells

Author: Rolf A. Brekken et al.

Session/Abstract ID: 602

The presentation will be made available on BerGenBio’s website, under ‘Presentations’.

On November 9, 2021 Applied DNA Sciences, Inc. (NASDAQ: APDN) (Applied DNA or the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing and nucleic acid-based technologies, reported the publication of a study in Molecular Therapy: Methods and Clinical Development on a methodology for the manufacture of novel types of CAR constructs that employ the Company’s LinearDNA as part of a manufacturing process for the efficient generation of CD19-specific CAR T-cells (CAR19 T-cells) based on co-electroporation of a LinearDNA transposon and mRNA encoding of piggyBac transposase (Press release, Applied DNA Sciences, NOV 9, 2021, View Source [SID1234594870]). PCR-produced LinearDNA is manufactured by LineaRx, the Company’s majority-owned subsidiary, to serve as a pure, fast, and flexible alternative to plasmid DNA (pDNA) for biotherapeutic applications.

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The study, titled "Enzymatically produced piggyBac transposon vectors for efficient non-viral manufacturing of CD19-specific CAR T cells", details the utility of LinearDNA in the cost-effective production of preclinical CAR T cells. Its authors, members of the Institute of Hematology and Blood Transfusion (ÚHKT) in Prague, Czechia, and the Faculty of Natural Sciences at Charles University, also in Prague, propose that the combination of LinearDNA and a transposon/transposase system offers therapy developers an effective research tool for making experimental CAR T cells rapidly and efficiently without the need for complicated virus production or the use of pDNA.

Pavel Otáhal, contributing author and Head of the Gene Immunotherapy Research Department at ÚHKT, stated, "Our study compares the manufacture of CAR19 T-cells via PCR-made transposon DNA (LinearDNA) with mRNA encoding of the transposase against a conventional plasmid approach. We found CAR T efficacy of the LinearDNA system versus the plasmid system to be identical. Further, we found no mutations in the coding sequence of LinearDNA and with >99% purity that obliviated the need for purification typical of a plasmid approach. As an institution dedicated to diagnosing and treating serious blood diseases and with the ability to pursue investigational medicines from development to manufacture and clinical trial for patients who have exhausted all approved treatment options, having a cost-effective and rapid production chain is integral to ÚHKT’s mission. We find LinearDNA to be an excellent platform for CAR T-cell therapy development."

Dr. James A. Hayward, president and CEO of Applied DNA, said, "The clinical successes of CAR T-cell therapy against blood cancers have been impressive, though limited by the complex production of viral vectors that are currently needed for T-cell genetic transformation and the use of pDNA. These manufacturing complexities have likewise hindered research on CAR T-cell therapies. As described in the publication, the use of LinearDNA, coupled with non-viral transfection systems, we believe, overcomes many of the existing manufacturing complexities associated with pDNA and viral vectors, thereby offering therapy developers a rapid and cost-effective tool for manufacturing preclinical CAR T cells. The authors’ findings as it relates to LinearDNA coincide with the industry’s growing interest in alternatives to pDNA for CAR T-cell therapies with approximately 50% of recent CRO orders coming from CAR T cell developers."

The detailed study write-up can be found at: Molecular Therapy: Methods and Clinical Development, the leading journal for research in the areas of gene transfer, vector development and design, stem cell manipulation, development of gene-, peptide-, protein-, oligonucleotide-, and cell-based therapeutics to correct genetic and acquired diseases, vaccine development, preclinical target validation, safety/efficacy studies, and clinical trials.