On February 24, 2022 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported financial results for the year ended December 31, 2021 (Press release, MacroGenics, FEB 24, 2022, View Source [SID1234608974]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited about our 2022 plans for our B7-H3-directed programs for the potential treatment of multiple solid tumors. We believe we are well-positioned to be a leader in this promising field and are prioritizing our efforts around B7-H3. First, I am pleased to share that later this quarter, we plan to meet with the U.S. Food and Drug Administration (FDA) to discuss the design of a potential registration-directed study of MGC018 in patients with metastatic castration-resistant prostate cancer (mCRPC). Second, we expect to initiate a study of MGC018 in combination with lorigerlimab, our bispecific DART molecule targeting PD-1 and CTLA-4, in the coming weeks. And third, during the second half of this year, we intend to provide an update from a study of our second B7-H3 targeted molecule, enoblituzumab, being evaluated in combination with two of our checkpoint molecules in front-line squamous cell carcinoma of the head and neck (SCCHN). Beyond these B7-H3 programs, we are advancing several of our other clinical-stage molecules and have a variety of ongoing preclinical activities intended to expand our pipeline of differentiated investigational product candidates for the potential treatment of cancer," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics.

Updates on Proprietary Programs

B7-H3 Programs: MacroGenics is developing two investigational, clinical product candidates that target B7-H3, an antigen with broad expression across multiple solid tumor types and a member of the B7 family of molecules involved in immune regulation. Recent highlights for these two molecules include:

MGC018 is an antibody-drug conjugate (ADC) that targets B7-H3. MacroGenics presented encouraging preliminary clinical results from an ongoing Phase 1/2 study of MGC018 in patients with solid tumors at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) meetings in 2021. The Phase 1/2 study expansion cohorts are fully enrolled for patients with mCRPC (n=40) and smaller cohorts of patients (n=approximately 20 each) with non-small cell lung cancer (NSCLC), melanoma and triple negative breast cancer (TNBC), while the Company continues to recruit patients for the SCCHN cohort. MacroGenics plans to meet with FDA later this quarter to discuss its development strategy in mCRPC. In addition, the Company intends to provide an update on clinical data from the dose expansion cohorts in the second half of 2022 as the data further mature. Finally, beyond monotherapy, the Company expects to initiate a combination study of MGC018 with lorigerlimab across multiple indications in the coming weeks.

Enoblituzumab is an Fc‐engineered, monoclonal antibody (mAb) that targets B7‐H3. MacroGenics continues to recruit patients into its Phase 2 study of enoblituzumab in combination with retifanlimab, the Company’s investigational, anti-PD-1 antibody that was licensed to Incyte, in front-line patients with SCCHN who are PD-L1 positive and with tebotelimab in SCCHN patients who are PD-L1 negative. The Company expects to complete enrollment of the PD-L1 positive patient cohort during the first half of this year and provide an update on this cohort during the second half of the year. I-Mab, MacroGenics’ partner in Greater China, announced in December that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) approved its Investigational New Drug (IND) submission for the initiation of a Phase 2 trial in China for enoblituzumab in combination with pembrolizumab in patients with solid tumors, including NSCLC, urothelial carcinoma and other selected cancers.
DART Molecules for Immune Checkpoint Blockade: MacroGenics is studying multiple investigational, PD-1-directed programs to provide further differentiation from existing PD-1-based treatment options and enable combination opportunities across the Company’s portfolio. Recent highlights include:

Lorigerlimab (formerly MGD019) is a bispecific, tetravalent DART molecule targeting PD-1 and CTLA-4. MacroGenics is conducting a Phase 1/2 dose expansion study in cohorts of patients with microsatellite stable colorectal cancer (MSS CRC), mCRPC, melanoma and checkpoint-naïve NSCLC. The Company anticipates sharing data from this ongoing study in the second half of 2022. As described above, MacroGenics expects to initiate a dose escalation study of MGC018 in combination with lorigerlimab in the coming weeks.

Tebotelimab is a bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab was evaluated in a Phase 1/2 dose expansion study in several tumor types and is currently being studied in combination with enoblituzumab in SCCHN. The Company expects to provide an update on potential future development plans for tebotelimab in the second half of 2022. MacroGenics’ partner in Greater China, Zai Lab, recently informed the Company that it has decided to discontinue development of tebotelimab for indications it was enrolling in its territory and is evaluating future development plans in other indications.
Bispecific CD123 × CD3 DART molecule: MacroGenics has prioritized the development of MGD024, its investigational, next-generation CD123 × CD3 DART molecule, and will discontinue the development of flotetuzumab. Recent updates of these DART molecules include:

MGD024 is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. In November, MacroGenics announced submission of an IND application for MGD024 to FDA. At the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December, MacroGenics presented preclinical data from the combination of MGD024 with standard-of-care agents used to treat CD123-positive hematological malignancies. The Company expects to initiate a Phase 1 dose escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia (AML), pending IND clearance by FDA.

Flotetuzumab is the Company’s first-generation, investigational, bispecific CD123 × CD3 DART molecule. An interim efficacy threshold from the single-arm study evaluating flotetuzumab in patients who were refractory to induction therapy was met with manageable safety. However, the Company has recently decided to prioritize the development of MGD024 and discontinue development of flotetuzumab, in view of the Company’s belief that MGD024 may offer certain advantages over flotetuzumab, including easier dose administration and a more facile means to combine with other agents.
Margetuximab is an Fc-engineered mAb that targets the HER2 oncoprotein, which is expressed by certain breast, gastroesophageal and other solid tumor cells. MARGENZA (margetuximab-cmkb) was launched in March 2021 by MacroGenics and its commercial partner, Eversana Life Science Services, LLC, for the treatment of adult patients with metastatic HER2-positive breast cancer, in combination with chemotherapy, who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. In January 2022, Zai Lab announced that the China NMPA accepted the New Drug Application (NDA) for margetuximab for the treatment of the same HER2-positive breast cancer indication.

Zai Lab recently informed MacroGenics that they have decided to discontinue enrollment of Module B of the MAHOGANY study in gastric cancer based on their review of both the clinical data and the changing treatment landscape. MacroGenics previously announced in November 2021 that the Company had decided to discontinue enrollment of Module A of the MAHOGANY study.

Selected Partnered Program Updates:

IMGC936 is an investigational ADC that targets ADAM9, a cell surface protein over-expressed in several solid tumor types, and is being developed jointly under a 50/50 collaboration with ImmunoGen, Inc. Under the collaboration, ImmunoGen is leading clinical development of IMGC936 in a Phase 1 clinical trial evaluating safety and pharmacokinetics in multiple solid tumors and has indicated they anticipate disclosing initial data in 2022.

Teplizumab is an investigational, anti-CD3 monoclonal antibody acquired from MacroGenics by Provention Bio, Inc. under an asset purchase agreement in 2018 for which MacroGenics is entitled to receive future milestone payments and royalties on net sales. Provention is developing teplizumab for the treatment of type 1 diabetes (T1D). On February 22, 2022, Provention announced that it had resubmitted the Biologics License Application (BLA) for teplizumab for the delay of clinical T1D in at-risk individuals. The BLA resubmission followed Provention’s Type B meeting with FDA earlier in the year.
2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2021, were $243.6 million, compared to $272.5 million as of December 31, 2020.
Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $77.4 million for the year ended December 31, 2021, compared to total revenue of $104.9 million for the year ended December 31, 2020. Revenue for the year ended December 31, 2021 included $12.3 million net sales of MARGENZA.
R&D Expenses: Research and development expenses were $214.6 million for the year ended December 31, 2021, compared to $193.2 million for the year ended December 31, 2020. The increase was primarily related to development, manufacturing and clinical trial costs related to MGC018, as well as other preclinical molecules and increased clinical expenses related to enoblituzumab and lorigerlimab. These increases were partially offset by decreased development and manufacturing costs related to retifanlimab for Incyte and decreased clinical costs and BLA support for margetuximab.
SG&A Expenses: Selling, general and administrative expenses were $63.0 million for the year ended December 31, 2021, compared to $42.7 million for the year ended December 31, 2020. The increase was primarily related to the MARGENZA launch, as well as labor-related costs and legal expenses.
Net Loss: Net loss was $202.1 million for the year ended December 31, 2021, compared to net loss of $129.7 million for the year ended December 31, 2020.
Shares Outstanding: Shares outstanding as of December 31, 2021 were 61,307,428.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities as of December 31, 2021, plus anticipated and potential collaboration payments, and product revenues should enable it to fund its operations through 2023. Such guidance does not reflect anticipated expenditures related to the potential late-stage development of MGC018 in mCRPC or further expansion of studies currently ongoing.
Conference Call Information

MacroGenics will host a conference call today at 4:30 p.m. (ET) to discuss financial results for the year ended December 31, 2021 and provide a corporate update. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 1067087.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

On February 24, 2022 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported fourth quarter and full year 2021 financial results and provided a corporate update (Press release, Kura Oncology, FEB 24, 2022, View Source [SID1234608973]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have made meaningful advancements across our programs during the past year, and we begin 2022 with significant momentum, resources and enthusiasm," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "By mid-2022, we expect to have three independent drug development programs with potential to create value in both solid and liquid tumor indications with high unmet need. We anticipate meaningful data catalysts for each of these programs in the next six to 24 months, beginning with top-line data from our KOMET-001 Phase 1b study. And we approach these catalysts from a position of strength, with an experienced team and more than $500 million in cash."

Recent Highlights

Patient enrollment continues in KOMET-001 Phase 1b study of ziftomenib (KO-539) – In January 2022, Kura received authorization from the U.S. Food and Drug Administration (FDA) to proceed with its KOMET-001 trial of ziftomenib (formerly KO-539) in patients with relapsed or refractory acute myeloid leukemia (AML), following agreement with the FDA on an enhanced mitigation strategy for differentiation syndrome. Differentiation syndrome is known to be an on-target effect associated with a number of therapeutic agents, including menin inhibitors, which may induce differentiation of leukemic blasts. Patients already enrolled in the Phase 1b expansion cohorts were eligible to remain on study during the partial clinical hold and enrollment of new patients has resumed.

Multiple milestones and data readouts from KOMET-001 expected in 2022 – Kura expects to complete enrollment of 24 patients in the Phase 1b study of ziftomenib by the second quarter of 2022, after which it will assess the patients in each expansion cohort for safety and tolerability, pharmacokinetics and exposure, as well as efficacy. The Company expects to identify the recommended Phase 2 dose for ziftomenib and report top-line data from the Phase 1b study by the third quarter of 2022, with updated data from KOMET-001 reserved for a medical meeting in the fourth quarter of 2022. Meanwhile, Kura continues to add sites in the U.S. and Europe in anticipation of the subsequent Phase 2 registration-enabling portion of KOMET-001.

First patients dosed in Phase 1/2 trial of tipifarnib plus alpelisib in HNSCC – Last year, Kura announced a clinical collaboration with Novartis to evaluate the combination of tipifarnib and the PI3Kα inhibitor alpelisib in patients with head and neck squamous cell carcinoma (HNSCC). The Company believes this combination has the potential to increase the total addressable population for tipifarnib to as much as 50% of patients with HNSCC. In December 2021, the first patient was dosed in a Phase 1/2 clinical trial (KURRENT) of tipifarnib in combination with alpelisib. The initial cohort includes patients who have PIK3CA-dependent HNSCC. The Company expects to initiate an HRAS overexpression cohort in KURRENT by the third quarter of 2022.

Preclinical data supporting next-generation FTI program at AACR (Free AACR Whitepaper) – Kura’s next-generation farnesyl transferase inhibitor (FTI) program is designed to target novel farnesylated targets and address large solid tumor indications of high unmet need through combination regimens, with a focus on delaying the onset of drug resistance. An abstract from one of the Company’s academic collaborators, with preclinical data supporting the first opportunity in non-small cell lung cancer (NSCLC), has been accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2022. Kura plans to perform initial clinical evaluation with tipifarnib in NSCLC while continuing its IND-enabling studies of KO-2806, the lead development candidate in the Company’s next-generation FTI program.
Financial Results

Research and development expenses for the fourth quarter of 2021 were $21.0 million, compared to $17.5 million for the fourth quarter of 2020. Research and development expenses for the full year 2021 were $84.7 million, compared to $60.4 million for the prior year.

General and administrative expenses for the fourth quarter of 2021 were $12.1 million, compared to $8.8 million for the fourth quarter of 2020. General and administrative expenses for the full year 2021 were $46.5 million, compared to $31.5 million for the prior year.

Net loss for the fourth quarter of 2021 was $32.7 million, compared to a net loss of $26.2 million for the fourth quarter of 2020. Net loss for the full year 2021 was $130.5 million, compared to a net loss of $89.6 million for the prior year. Net loss for the fourth quarter and full year 2021 included non-cash share-based compensation expense of $6.4 million and $23.6 million, respectively, $3.7 million and $12.8 million for the same periods in 2020.

Cash, cash equivalents and short-term investments totaled $518.0 million as of December 31, 2021, compared with $633.3 million as of December 31, 2020. Management expects that current cash, cash equivalents and short-term investments will be sufficient to fund current operations into 2024.
2022 Milestones

Complete enrollment of 24 patients in the KOMET-001 Phase 1b expansion cohorts by the second quarter.

Identify the recommended Phase 2 dose of ziftomenib (KO-539) and report top-line data from the Phase 1b expansion cohorts by the third quarter.

Present updated data from KOMET-001 at a medical meeting in the fourth quarter.

Initiate the HRAS overexpression cohort in the KURRENT trial of tipifarnib plus alpelisib by the third quarter.

Report preclinical data supporting the use of a FTI to delay the onset of drug resistance in NSCLC in the second quarter.

Submit an IND application for KO-2806 by the end of the year.
Conference Call and Webcast

Kura’s management will host a webcast and conference call at 4:30 p.m. ET / 1:30 p.m. PT today, February 24, 2022, to discuss the financial results for the fourth quarter and full year 2021 and to provide a corporate update. The live call may be accessed by dialing (877) 516-3514 for domestic callers and (281) 973-6129 for international callers and entering the conference code: 8645626. A live webcast and archive of the call will be available online from the investor relations section of the company website at www.kuraoncology.com.

On February 24, 2022 Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to transforming the lives of those affected by cancer and other serious diseases, reported recent business progress and fourth-quarter and full-year 2021 financial results (Press release, Kronos Bio, FEB 24, 2022, View Source [SID1234608972]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We had a successful year, marked by the significant progress we made across our clinical pipeline, including initiating our registrational Phase 3 AGILITY study of entospletinib, and initiating our Phase 1/2 study of KB-0742 and subsequently reporting positive initial results from the KB-0742 study," said Norbert Bischofberger, Ph.D., president and chief executive officer of Kronos Bio. "We expect to announce the initiation of our third clinical trial later this quarter. We continue to dose-escalate KB-0742 and anticipate reaching the recommended Phase 2 dose and sharing additional Phase 1 data in the fourth quarter."
KB-0742 Update
•Kronos Bio is continuing to enroll patients in the Phase 1/2 trial of KB-0742. KB-0742 is the company’s internally discovered, highly selective, orally administered cyclin dependent kinase 9 (CDK9) inhibitor being developed to treat MYC-amplified and other transcriptionally addicted solid tumors. Kronos Bio reported positive initial data from the study last year and is continuing to dose escalate.
•The company expects to announce a recommended Phase 2 dose and announce updated Phase 1 data in Q4 2022.
•While the first stage of the study does not mandate enrollment of patients with MYC amplification or other evidence of transcriptional addiction, as the trial nears pharmacologically active dose levels, the company anticipates increased enrollment of patients who may be more likely to respond to CDK9 inhibition.
SYK Inhibitor Program Update
•Kronos Bio expects to dose the first patient in a Phase 1b/2 clinical trial of lanraplenib in the first quarter of 2022. This trial will evaluate lanraplenib in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML) in combination with the current standard of care, gilteritinib.
•To better focus on and prioritize the company’s resources on the areas of highest unmet need, Kronos Bio has decided not to proceed at this time with its previously planned second Phase 1b/2 clinical trial of lanraplenib in combination with venetoclax/azacitidine.
Fourth-Quarter Company Highlights
•Kronos Bio dosed the first patient in the registrational Phase 3 AGILITY clinical trial of entospletinib, a selective inhibitor targeting spleen tyrosine kinase (SYK), in combination with standard of care anthracycline and cytarabine (7+3) chemotherapy. This trial is the first in AML to

Exhibit 99.1
use measurable residual disease (MRD) as the primary endpoint and has the potential to support accelerated approval of entospletinib by the U.S. Food and Drug Administration as a treatment for patients newly diagnosed with NPM1-mutated AML who are fit for intensive induction. The company expects to share data from the trial in the second half of 2023.
•Kronos Bio announced positive data from the ongoing Phase 1/2 clinical trial of KB-0742. The initial analysis of the ongoing dose escalation stage of the trial demonstrated a differentiated pharmacokinetic profile and evidence of target engagement for KB-0742.
•Kronos Bio appointed Roshawn Blunt to its Board of Directors. Ms. Blunt has decades of experience in the commercialization of new therapeutics, including oncology medicines, with expertise in patient access, reimbursement and health policy. Her expertise will be highly relevant as Kronos Bio advances its lead programs.
•Kronos Bio announced its multi-year collaboration with Tempus Labs, Inc., a leader in artificial intelligence and precision medicine, during the fourth quarter. The agreement provides Kronos Bio with access to real-world patient genomic and transcriptomic data and data analytics tools, with the goal of accelerating the development of the company’s current and future clinical portfolio.
Fourth-Quarter and Full-Year 2021 Financial Highlights
•Cash, Cash Equivalents and Investments: With its ongoing and currently planned clinical programs and $339.5 million in cash, cash equivalents and investments as of December 31, 2021, the company anticipates sufficient resources to fund its planned operations into the second half of 2024.

•R&D Expenses: Research and development expenses were $50.8 million for the fourth quarter of 2021, which includes non-cash stock-based compensation expense of $3.4 million. For the full year of 2021, research and development expenses were $112.9 million, which includes non-cash stock-based compensation expense of $13.0 million.

Research and development expenses for the fourth quarter included the $29.0 million milestone paid to Gilead Sciences upon initiation of Kronos Bio’s registrational Phase 3 clinical trial of entospletinib in December 2021.

•G&A Expenses: General and administrative expenses were $11.6 million for the fourth quarter of 2021, which includes non-cash stock-based compensation expense of $4.0 million. For the full year of 2021, general and administrative expenses were $38.5 million, which includes non-cash stock-based compensation expense of $13.3 million.

•Net Loss: Net loss for the fourth quarter of 2021 was $62.3 million, or $1.13 per share, including non-cash stock-based compensation of $7.4 million. Net loss for the full-year 2021 was $151.1 million, or $2.76 per share, including non-cash stock-based compensation expense of $26.2 million.

On February 24, 2022 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported that the company will participate in Cowen’s 42nd Annual Health Care Conference which is taking place virtually on March 7 – 9, 2022 (Press release, Kineta, FEB 24, 2022, View Source;utm_medium=rss&utm_campaign=kineta-invited-to-participate-in-the-cowen-42nd-annual-health-care-virtual-conference [SID1234608971]). Members of Kineta’s management team will be available for one-on-one meetings during the conference. The conference incorporates presentations, fireside chats and innovative panel discussions hosted by members of the Cowen research team that focus on various aspects of the health care industry.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On February 24, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported fourth quarter and full year 2021 financial results and corporate updates (Press release, Iovance Biotherapeutics, FEB 24, 2022, View Source [SID1234608970]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "Throughout 2021, we continued to build upon the strength of clinical data for Iovance TIL therapy in multiple solid tumor types and treatment settings. Highlights included long-term clinical data for one-time treatment with lifileucel in metastatic melanoma, the potential to increase response rates for TIL therapy in combination with pembrolizumab as an earlier treatment for melanoma, cervical and head and neck cancers, as well as an important proof-of-concept for Iovance TIL therapy in non-small cell lung cancer. We also advanced our genetically modified TIL pipeline and expect to initiate our first clinical study of a gene-edited TIL product candidate later this year. Our top priority remains our ongoing work to address feedback from the U.S. Food and Drug Administration (FDA) regarding the potency assays for lifileucel to support our planned biologics license application (BLA) submission in the first half of this year. We remain increasingly confident in the broad potential for TIL as the next class of paradigm-shifting therapy for cancer patients with significant unmet need."

Full Year 2021 Highlights and Recent Corporate Updates

Regulatory

Potency assays for lifileucel: Following FDA feedback regarding the potency assays for lifileucel, Iovance has continued ongoing work developing and validating its potency assays and has engaged in discussions with the FDA during the second half of 2021. The anticipated BLA submission for lifileucel continues to be planned for the first half of 2022. Resolution of the potency assay for lifileucel in melanoma is also a key step towards regulatory plans in other indications.
U.S. FDA Fast Track Designation for lifileucel in combination with pembrolizumab in metastatic melanoma: The FDA granted fast track designation for lifileucel in combination with pembrolizumab for the treatment of immune checkpoint inhibitor (ICI) naïve (frontline) metastatic melanoma based on the unmet medical need and potential advantages for this combination over available care.
Clinical

Iovance TIL therapy (lifileucel) in metastatic melanoma:
Lifileucel in late line (post-anti-PD-1) melanoma: Follow up data as assessed by investigators from Cohort 2 (n=66) in the C-144-01 study of lifileucel in advanced melanoma were presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting. The overall response rate (ORR) was 36.4% (4.5% complete response rate and 31.8% partial response rate) and median duration of response (DOR) was not reached at 33.1 months of median study follow up. Iovance expects to report clinical data from the pivotal melanoma Cohort 4 as assessed by an independent review committee (IRC) in 2022 in connection with its BLA submission.
Lifileucel in combination with pembrolizumab in early line (anti-PD-1 naïve) melanoma (Cohort 1A in the IOV-COM-202 study): Initial clinical data were presented at ASCO (Free ASCO Whitepaper) 2021 and updated results were presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021. The updated ORR was 60% and the complete response rate was 30% at a median follow up of 11.5 months in Cohort 1A (n=10). Based on these results, Iovance intends to expand Cohort 1A and define a development strategy in early line melanoma in 2022.

Iovance TIL therapy (LN-145) in non-small cell lung cancer (NSCLC):

LN-145 monotherapy in metastatic NSCLC (mNSCLC): Results from Cohort 3B in the IOV-COM-202 study were highlighted at SITC (Free SITC Whitepaper) 2021. LN-145 showed a 21.4% ORR in the full analysis set (n=28) and 25% in the efficacy-evaluable set (n=24). One complete response and one partial response were ongoing at 20.7 months and 3.0 months, respectively, at a median study follow up of 9.8 months. These results demonstrated activity for TIL therapy in heavily pretreated mNSCLC patients who received one or more prior systemic therapies, including anti-PD-1 therapy, and support the ongoing development strategy for LN-145 in second line mNSCLC patients in the IOV-LUN-202 study.
LN-145 in second-line mNSCLC: Enrollment is ongoing at more than 30 active clinical sites in the U.S., Canada and Europe for the IOV-LUN-202 study of LN-145 in patients with mNSCLC following a single line of approved systemic therapy. Iovance is engaged in discussions with the FDA about IOV-LUN-202 and intends to incorporate FDA feedback into the study design to support registration.

Lifileucel in cervical cancer: The C-145-04 study is investigating lifileucel for the treatment of metastatic cervical cancer patients following chemotherapy (Cohort 1), after chemotherapy and anti-PD-1/PD-L1 therapy (Cohort 2), and in combination with pembrolizumab in patients who have not had therapy for advanced disease (Cohort 3).

Lifileucel monotherapy in advanced cervical cancer: Iovance is engaged in regulatory discussions about a potential BLA for lifileucel in cervical cancer and intends to execute an updated registrational strategy based on FDA dialogue and feedback.
Lifileucel in combination with pembrolizumab in early line cervical cancer: Initial results from Cohort 3 (n=14) in the C-145-04 study were presented at SITC (Free SITC Whitepaper) 2021 and demonstrated an ORR of 57.1% at a median follow up of 7.6 months.
Iovance TIL therapy combinations in additional solid tumor cancers: In Cohort 2A of the IOV-COM-202 study, Iovance is also investigating TIL therapy in combination with pembrolizumab in patients with head and neck squamous cell carcinoma (HNSCC) who are naïve to therapy with ICIs. Updated Cohort 2A data were presented at SITC (Free SITC Whitepaper) 2021 and demonstrated a 38.9% ORR (n=18) at a median study follow up of 7.8 months. The IOV-COM-202 study is also investigating TIL combinations in patients with NSCLC including TIL therapy plus pembrolizumab (Cohort 3A) and TIL plus ipilimumab/nivolumab (Cohort 3C).
Next-Generation Genetically Modified TIL Products and Research Programs

Iovance expects to initiate its first clinical study of a genetically modified TIL product candidate in 2022. The lead program, designated IOV-4001, leverages the TALEN technology licensed from Cellectis S.A. to inactivate PD-1 expression in the TIL product.
Additional targets for genetic modification using the TALEN technology, including double knock-out programs, are in preclinical development.
Approaches to increase TIL potency using CD39/69 double negative TILs and gene knock-in targets are also in preclinical development.
Accepted abstracts at the upcoming Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR Tandem Meetings, April 23-26, 2022, describe TIL products manufactured from cryopreserved tumor samples shipped from Australia and a potential approach to optimize TIL memory-like phenotype and increase functionality during the manufacturing process.
Iovance continues to advance additional research and preclinical studies of next generation TIL therapies and related technologies, including a novel IL-2 analog (IOV-3001).
Manufacturing

Iovance Cell Therapy Center (iCTC): Commissioning activities were completed and clinical manufacturing of TIL product commenced at the iCTC, Iovance’s 136,000 square foot cell therapy manufacturing facility, in the third quarter of 2021. Commercial manufacturing remains on track to commence with a potential BLA approval.
Generation 3 (Gen 3) manufacturing: TIL product manufactured using a shorter 16-day third generation process (Gen 3) is being investigated in cohorts of metastatic melanoma patients in the IOV-COM-202 study as well as NSCLC patients in the IOV-LUN-202 study.
Corporate

Cash position of $602.1 million at December 31, 2021 is expected to be sufficient into 2024.
A strong organization of approximately 350 employees with an average of more than four years of cell therapy experience is in place to advance research, development, manufacturing, and commercial launch preparations.
Iovance continues to expand its intellectual property portfolio and currently owns more than 35 granted or allowed U.S. and international patents for TIL compositions and methods of treatment and manufacturing in a broad range of cancers. Iovance’s Gen 2 patent rights are expected to provide exclusivity into 2038. Iovance’s portfolio also includes patent applications and granted patents directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic TIL modifications, tumor digest and fragment compositions and methods (including cryopreservation), and combinations of checkpoint inhibitors and TIL products.
Fourth Quarter and Full Year 2021 Financial Results

Iovance had $602.1 million in cash, cash equivalents, investments and restricted cash at December 31, 2021 compared to $635.0 million at December 31, 2020. The cash position is expected to be sufficient to fund current and planned operations into 2024.

Jean-Marc Bellemin, Chief Financial Officer, stated, "With late-stage clinical assets in our pipeline, as well as a strong balance sheet and investments focused on launch preparations, we are well positioned to execute our operating plan. We are confident in our prospects to deliver new treatment options to patients with great unmet need while enhancing shareholder value."

Net loss for the fourth quarter ended December 31, 2021, was $99.3 million, or $0.63 per share, compared to a net loss of $68.4 million, or $0.47 per share, for the fourth quarter ended December 31, 2020. Net loss for the full year period ended December 31, 2021, was $342.3 million, or $2.23 per share, compared to a net loss of $259.6 million, or $1.88 per share, for the full year period ended December 31, 2020.

Research and development expenses were $75.6 million for the fourth quarter ended December 31, 2021, an increase of $23.1 million compared to $52.5 million for the fourth quarter ended December 31, 2020. Research and development expenses were $259.0 million for the full year period ended December 31, 2021, an increase of $57.3 million compared to $201.7 million for the full year ended December 31, 2020.

The increase in research and development expenses in the fourth quarter 2021 over the prior year period was primarily attributable to an increase in costs associated with growth of the internal research and development team, including stock-based compensation expense, and increases in clinical trial costs and facility related costs associated with the iCTC. The increase in research and development expenses in the full year 2021 over the prior full year period was primarily attributable to growth of the internal research and development team and an increase in clinical trial costs and facility related costs associated with the iCTC.

General and administrative expenses were $23.8 million for the fourth quarter ended December 31, 2021, an increase of $7.7 million compared to $16.1 million for the fourth quarter ended December 31, 2020. General and administrative expenses were $83.7 million for the full year period ended December 31, 2021, an increase of $23.5 million compared to $60.2 million for the full year ended December 31, 2020.

The increases in general and administrative expenses in the fourth quarter and full year 2021 compared to the prior year periods were primarily attributable to an increase in costs associated with growth of the internal general and administrative team, including stock-based compensation expense, and an increase in intellectual property filing related costs.

Webcast and Conference Call

Iovance will host a conference call today at 4:30 p.m. ET to discuss the fourth quarter and full year 2021 financial results and corporate updates. The conference call dial-in numbers are 1-(844) 646-4465 (domestic) or 1-(615) 247-0257 (international) and the access code is 2877242. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.