On November 3, 2021 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a clinical-stage company advancing an integrated and sustainable pipeline of genetic therapies for rare childhood disorders, reported its financial results for the quarter ending September 30, 2021 and updates on the Company’s key pipeline developments, business operations, and upcoming milestones (Press release, Rocket Pharmaceuticals, NOV 3, 2021, View Source [SID1234594271]).

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"We are excited about the strong progress we made in the third quarter as we initiated treatment in our trial of RP-A501 for Danon Disease in the low-dose (6.7e13 vg/kg) pediatric patient cohort," said Gaurav Shah, M.D., Chief Executive Officer of Rocket Pharma. "I am proud of our team’s collaboration with the FDA, through which we were able to swiftly resolve the clinical hold on the Danon trial and resume this highly important work on behalf of Danon patients. We are gearing up for the remainder of 2021 and look forward to reporting a comprehensive clinical update on our Phase I trial in Danon Disease this month at the AHA Scientific Sessions as well as key updates on all five of our first-in-class gene therapy programs throughout the fourth quarter."

Dr. Shah continued, "We are equally excited about the progress of our LAD-I program, where we completed treatment for all nine patients in the RP-L201 Phase 1/2 clinical trial and presented positive interim data updates on the initial seven patients at the ESGCT Congress in October. Based on the data presented from these seven patients, RP-L201 continues to demonstrate a favorable safety profile and preliminary clinical benefit in patients with severe LAD-I. We will share additional clinical data from the LAD-I trial at the 63rd ASH (Free ASH Whitepaper) Annual Meeting in December, where we will also report clinical updates on our Fanconi Anemia and PKD programs. I am proud of the Rocket team’s unwavering dedication to developing and bringing life-changing curative therapies to patients with rare diseases."

Key Pipeline and Operational Updates

Danon Disease:

Initiated pediatric patient treatment in Phase 1 trial of RP-A501 for the treatment of Danon Disease. Rocket has resumed patient enrollment and initiated treatment in the low-dose (6.7e13 vg/kg) pediatric patient cohort. A comprehensive clinical update is anticipated at the American Heart Association (AHA) Scientific Sessions 2021 being held virtually November 13-15, 2021.
Presented previously disclosed data from ongoing RP-A501 Phase 1 trial in Danon Disease at HFSA. The late-breaking oral presentation at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2021 overviewed data from the low-dose (6.7e13 vg/kg) adult cohort which demonstrated RP-A501 was well tolerated and showed progressive and durable clinical benefit.
Leukocyte Adhesion Deficiency-I (LAD-I):

Presented positive interim data updates from RP-L201 LAD-I trial at ESGCT. The oral presentation included data from the initial seven patients with severe LAD-I who were treated with RP-L201 in the Phase 1/2 trial. The safety profile of RP-L201 appears favorable with all infusions well tolerated and no drug product-related serious adverse events. Preliminary efficacy was evident in all seven patients, including two patients with at least 12 months of follow-up. All seven patients demonstrated durable neutrophil CD18 expression that exceeded the 4-10% threshold associated with survival into adulthood and consistent with reversal of the severe LAD-I phenotype. Peripheral blood vector copy number (VCN) levels have been stable and in the 0.5 – 2.5 copy per genome range. No patients have had LAD-I related infections requiring hospitalization subsequent to hematopoietic reconstitution post RP-L201. Additional clinical data are anticipated at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held December 11-14, 2021.
Fanconi Anemia (FA):

Presented previously disclosed clinical data from RP-L102 Fanconi Anemia (FA) program at ESGCT. The oral presentation included data for nine pediatric patients treated with RP-L102, Rocket’s ex vivo lentiviral gene therapy candidate, in the ongoing clinical trials. RP-L102 demonstrated a highly favorable safety profile with all subjects being treated without conditioning and with no sign of dysplasia or other concerning features. RP-L102 showed evidence of preliminary engraftment in at least six of nine patients. A clinical update is anticipated at the 63rd ASH (Free ASH Whitepaper) Annual Meeting being held December 11-14, 2021.
Pyruvate Kinase Deficiency (PKD):

Presented incremental updates from RP-L301 Pyruvate Kinase Deficiency (PKD) program at ESGCT. The oral presentation included data from two adult patients treated with RP-L301, Rocket’s ex vivo lentiviral gene therapy candidate, in the ongoing Phase 1 trial. The safety profile of RP-L301 appears favorable with no infusion-related serious adverse events at up to 9 months post-infusion. Both patients have normalized hemoglobin, improved hemolysis markers and no red blood cell transfusion requirements post-engraftment, as well as no hospitalizations post-hospital discharge. A clinical update is anticipated at the 63rd ASH (Free ASH Whitepaper) Annual Meeting being held December 11-14, 2021.
Published peer-reviewed studies supporting scientific rationale for clinical results observed to date in RP-L301 trial. "Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment" was published in Molecular Therapy: Methods & Clinical Development. The studies demonstrate that in the murine model of PKD, reversion of the phenotype is seen when at least 20% of hematopoietic stem/progenitors are corrected, with comprehensive reversion seen when at least 30% of these progenitors are corrected. This provides meaningful scientific rationale for the clinical results that have been observed to date for the first two patients who have received RP-L301.
Infantile Malignant Osteopetrosis (IMO):

Presented preclinical data supporting ongoing RP-L401 Infantile Malignant Osteopetrosis (IMO) Phase 1 trial at ESGCT. The Phase 1 trial is designed to assess safety and tolerability, as well as preliminary efficacy, of RP-L401, Rocket’s ex vivo lentiviral gene therapy candidate. A clinical update on the Phase 1 trial is anticipated later in the fourth quarter.
Anticipated Milestones

Fanconi Anemia (RP-L102)
Updated "Process B" data (Q4 2021)
LAD-I (RP-L201)
Longer-term Phase 2 data (Q4 2021)
Danon Disease (RP-A501)
Longer-term Phase 1 data (Q4 2021)
PKD (RP-L301)
Longer-term Phase 1 data (Q4 2021)
IMO (RP-L401)
Phase 1 clinical update (Q4 2021)
Third Quarter Financial Results

Cash position. Cash, cash equivalents and investments as of September 30, 2021, were $421.5 million.
R&D expenses. Research and development expenses were $40.0 million for the three months ended September 30, 2021, compared to $21.7 million for the three months ended September 30, 2020, due to increase in manufacturing and development costs, an increase in new research agreements of $7.6 million in non-cash expenses, increases in compensation and benefits due to increased R&D headcount, and an increase in non-cash stock compensation expense.
G&A expenses. General and administrative expenses were $9.7 million for the three months ended September 30, 2021, compared to $5.7 million for the three months ended September 30, 2020, due to an increase in non-cash stock compensation expense, an increase in compensation and benefits expense due to increased G&A headcount and an increase in commercial preparation expenses.
Net loss. Net loss was $50.1 million or $0.79 per share (basic and diluted) for the three months ended September 30, 2021, compared to $29.1 million or $0.53 per share (basic and diluted) for the three months ended September 30, 2020.
Shares outstanding. 64,442,601 shares of common stock were outstanding as of September 30, 2021.
Financial Guidance

Rocket expects its balance in cash, cash equivalents and investments of $421.5 million as of September 30, 2021 to fund its operations into the second half of 2023, including the continued buildout and initiation of AAV cGMP manufacturing capabilities at our Cranbury, New Jersey R&D and manufacturing facility and continued development of our five clinical programs.

On November 3, 2021 Horizon Therapeutics plc (Nasdaq: HZNP) reported record third-quarter 2021 financial results and increased both its full-year 2021 net sales and adjusted EBITDA guidance (Press release, Horizon Therapeutics, NOV 3, 2021, View Source [SID1234594270]).

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"We generated record results in the third quarter and made significant progress executing our R&D strategy, further expanding our pipeline with five new programs," said Tim Walbert, chairman, president and chief executive officer, Horizon. "In addition to our strong commercial execution with TEPEZZA and KRYSTEXXA, our expanded pipeline positions us to drive future growth and diversification, as well as address the unmet medical needs of many people living with rare, autoimmune and severe inflammatory diseases around the world."

Third Quarter and Recent Company Highlights

Announced Five New R&D Programs and Highlighted Expanded Pipeline at Inaugural R&D Day: In September, the Company announced four new programs for its development-stage candidate daxdilimab (HZN-7734) in alopecia areata, discoid lupus erythematosus, dermatomyositis and lupus nephritis and one new program for its development-stage candidate dazodalibep (HZN-4920) in focal segmental glomerulosclerosis. The Company expects to initiate Phase 2 trials in each of these indications in 2022. The new programs, in addition to the Company’s R&D strategy and other key programs, were highlighted at the Company’s inaugural R&D Day in September.

Announced Positive Topline Data from KRYSTEXXA MIRROR Trial: In October, the Company announced positive topline results from the MIRROR Phase 4 randomized, placebo-controlled trial evaluating the use of KRYSTEXXA plus methotrexate. The MIRROR trial results demonstrated that 71 percent of patients who were randomized to receive KRYSTEXXA plus methotrexate achieved a complete response rate at Month 6 (p<0.001), a significant improvement from the 40 percent response rate in patients who were randomized to receive KRYSTEXXA plus placebo. In the Phase 3 clinical program, which evaluated KRYSTEXXA alone compared to placebo, 42 percent of patients receiving KRYSTEXXA achieved a complete response. The Company plans to submit a sBLA to the U.S. FDA in the first quarter of 2022. Full data from the trial is expected to be presented at future medical meetings. KRYSTEXXA plus immunomodulation is a core element of the Company’s strategy to maximize the value of KRYSTEXXA and enable more patients with uncontrolled gout to benefit from the medicine.

Initiated Enrollment in TEPEZZA Chronic TED Trial: In September, the first patient was enrolled in a Phase 4 randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of TEPEZZA for the treatment of chronic TED. TED is a serious, progressive and potentially vision-threatening rare autoimmune disease. It begins with an acute phase where inflammatory signs and symptoms, such as eye pain, swelling, proptosis (eye bulging) and diplopia (double vision), progress over time. The acute stage is followed by a chronic phase in which inflammation is no longer present or has markedly diminished; however, significant signs and symptoms may remain and continue to impact the quality of life. The objective of the trial is to generate clinical data to better inform physicians and payers about the safety and efficacy of TEPEZZA in patients with chronic TED. Results are expected in the second half of 2022.

Presented New UPLIZNA (inebilizumab-cdon) Data at Key Medical Meetings: New UPLIZNA data were presented at the 15th World Congress on Controversies in Neurology (CONy Virtual), including end-of-study data from the open-label extension period of the Phase 3 trial in patients with neuromyelitis optica spectrum disorder (NMOSD). The data indicated that UPLIZNA may provide durable efficacy and a favorable safety profile for African Americans with NMOSD. Multiple new data were also presented at the virtual 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October. Additionally, a new analysis of data from the Phase 3 trial was published in the Multiple Sclerosis Journal that highlighted a sustained effect on attack risk in people with NMOSD who were treated with UPLIZNA for four or more years.

Acquired Biologics Manufacturing Facility in Waterford, Ireland: In July, the Company completed the acquisition of a biologics drug product manufacturing facility in Waterford, Ireland. The Company intends to use the manufacturing facility to support the growth of the Company’s on-market medicines, including TEPEZZA, KRYSTEXXA and UPLIZNA, as well as development-stage biologics.

Continued to Demonstrate Gender and Ethnicity Pay Equity: A second study conducted by Aon, a leading compensation consulting firm, showed that Horizon continues to demonstrate both gender and ethnicity pay equity. This study was a follow-on study to the gender and pay ethnicity study Aon conducted in 2019. The Company maintained its gender and ethnicity pay equity despite having grown significantly in the two years since the first study, as well as having completed the acquisition of Viela Bio, which included the addition of a significant number of employees.

Multiple Additional Recognitions as a Best Workplace: In September, the Company was named one of the "2021 Best Workplaces for Women" by Fortune and Great Place to Work for the first time. In addition, the Company was also recognized as one of PEOPLE’s "100 Companies That Care" for the third year. In July, Fortune and Great Place to Work named the Company to the "Best Workplaces for Millennials" list for the second consecutive year and the Company was the highest ranked biotechnology company on the list. In addition, in October the Company was named one of the Top 100 Adoption-Friendly Workplaces by the Dave Thomas Foundation for Adoption for the third consecutive year. Most recently, Horizon was named to Newsweek’s inaugural "Most Loved Workplaces" list, ranking among the top 100 companies recognized for employee happiness and satisfaction at work and was the highest-ranked company in the biotechnology and pharmaceutical category. To date in 2021, the Company has received 11 workplace-related recognitions, reflecting the high level of engagement of its employees.
Key Clinical Development Programs

Daxdilimab (HZN-7734), an anti-ILT7 human monoclonal antibody that depletes certain dendritic cells. Depleting these cells may interrupt the cycle of inflammation that causes tissue damage in diseases such as lupus, and a variety of other autoimmune conditions.

Systemic Lupus Erythematosus (SLE) Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate daxdilimab in patients with SLE, a disease in which the body’s immune system attacks its own tissues and organs.

Alopecia Areata Trial: Phase 2 trial to evaluate daxdilimab in patients with alopecia areata, an autoimmune disorder characterized by nonscarring hair loss, expected to initiate in the first half of 2022.

Discoid Lupus Erythematosus (DLE) Trial:Phase 2 trial to evaluate daxdilimab in patients with DLE, a rare, chronic, inflammatory skin condition characterized by lesions that result in scarring, expected to initiate in the first half of 2022.

Lupus Nephritis Trial: Phase 2 trial to evaluate daxdilimab in patients with lupus nephritis, a rare, autoimmune disorder characterized by rashes, debilitating muscle weakness and interstitial lung disease, expected to initiate in the second half of 2022.

Dermatomyositis Trial: Phase 2 trial to evaluate daxdilimab in patients with dermatomyositis, a rare, autoimmune and inflammatory condition of the kidney, expected to initiate in the second half of 2022.

Dazodalibep (HZN-4920), a CD40 ligand antagonist that blocks T cell interaction with the CD40-expressing B cells, disrupting the overactivation of the CD40 ligand co-stimulatory pathway. Several autoimmune diseases are associated with the overactivation of this pathway.

Sjögren’s Syndrome Trial: Phase 2b randomized, placebo-controlled trial underway to evaluate dazodalibep in patients with Sjögren’s syndrome, a chronic, systemic autoimmune condition that impacts exocrine glands, including the salivary and tear glands.

Rheumatoid Arthritis Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate dazodalibep in patients with rheumatoid arthritis.

Kidney Transplant Rejection Trial: Phase 2 open-label trial underway to evaluate dazodalibep in kidney transplant rejection patients.

Focal Segmental Glomerulosclerosis (FSGS) Trial: Phase 2 trial to evaluate dazodalibep in patients with FSGS, a rare kidney disorder characterized by scarring of glomeruli, expected to initiate in the second half of 2022.

HZN-825, an oral lysophosphatidic acid receptor 1 (LPAR1) antagonist that prevents gene activation.

Diffuse Cutaneous Systemic Sclerosis Trial: Pivotal Phase 2b trial to evaluate HZN-825 in diffuse cutaneous systemic sclerosis, expected to initiate in the fourth quarter of 2021.

Interstitial Lung Disease Trial: Pivotal Phase 2b trial to evaluate HZN-825 in idiopathic pulmonary fibrosis, the most common form of interstitial lung disease, expected to initiate in the fourth quarter of 2021.

UPLIZNA, an anti-CD19 humanized monoclonal antibody that depletes B cells, including the pathogenic cells that produce autoantibodies.

Myasthenia Gravis Trial:Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with myasthenia gravis, a chronic, rare, autoimmune neuromuscular disease that affects voluntary muscles, especially those that control the eyes, mouth, throat and limbs.

IgG4-Related Disease Trial: Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with IgG4-related disease, which is a group of disorders marked by tumor-like swelling and fibrosis of affected organs, such as the pancreas, salivary glands and kidneys.

Kidney Transplant Desensitization Trial: Phase 2 open-label trial underway to evaluate UPLIZNA, dazodalibep or both in highly sensitized patients waiting for a kidney transplant.

TEPEZZA, an insulin-like growth factor type 1 receptor (IGF-1R) antagonist monoclonal antibody.

Chronic TED Trial: Phase 4 randomized, placebo-controlled trial initiated in September 2021 to evaluate TEPEZZA in chronic TED.

Subcutaneous (SC) Administration Trial:Phase 1 pharmacokinetic trial underway to explore SC administration of TEPEZZA.

Diffuse Cutaneous Systemic Sclerosis Exploratory Trial: Phase 1 exploratory trial to evaluate TEPEZZA in diffuse cutaneous systemic sclerosis expected to initiate in the fourth quarter of 2021.

KRYSTEXXA, a recombinant uricase enzyme that converts urate into a water-soluble liquid, allantoin, that can be easily excreted from the body.

MIRROR Trial: Phase 4 randomized, placebo-controlled trial to evaluate KRYSTEXXA plus methotrexate to increase the complete response rate in patients with uncontrolled gout. Topline results were announced on Oct. 25, 2021. The results demonstrated that 71 percent of patients who were randomized to receive KRYSTEXXA plus methotrexate achieved a complete response rate at Month 6 (p<0.001), a significant improvement from the 40 percent response rate in patients who were randomized to receive KRYSTEXXA plus placebo.

PROTECT Trial: Phase 4 open-label trial to evaluate KRYSTEXXA to improve management of uncontrolled gout in kidney transplant patients. This trial is completed, and final results will be presented at American Society of Nephrology (ASN) Kidney Week 2021 later this week.

Shorter Infusion Duration Trial: Phase 4 open-label trial underway to evaluate the impact of administering KRYSTEXXA plus methotrexate over a shorter infusion duration in patients with uncontrolled gout.

Monthly Dosing Trial:Phase 4 open-label trial underway to evaluate monthly dosing of KRYSTEXXA plus methotrexate in patients with uncontrolled gout.

Retreatment Trial: Phase 4 open-label trial underway to evaluate KRYSTEXXA plus methotrexate in patients who were not complete responders to KRYSTEXXA monotherapy.

HZN-1116 Autoimmune Disease Trial: Phase 1 trial initiated in July 2021 to evaluate HZN-1116, a monoclonal antibody, in patients with autoimmune diseases.
Third-Quarter Financial Results

Note: For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

Net Sales: Third-quarter 2021 net sales were $1.037 billion, an increase of 63 percent compared to the third quarter of 2020.

Gross Profit: Under U.S. GAAP, the third-quarter 2021 gross profit ratio was 75.7 percent compared to 76.2 percent in the third quarter of 2020. The non-GAAP gross profit ratio in the third quarter of 2021 was 85.4 percent compared to 86.7 percent in the third quarter of 2020.

Operating Expenses: R&D expenses were 9.0 percent of net sales and SG&A expenses were 34.7 percent of net sales. Non-GAAP R&D expenses were 7.2 percent of net sales and non-GAAP SG&A expenses were 29.0 percent of net sales.

Income Tax Expense (Benefit): On a GAAP basis in the third quarter of 2021, income tax benefit was $19.3 million. Third-quarter non-GAAP income tax expense was $73.8 million.

Net Income: In the third-quarter of 2021, net income on a GAAP and non-GAAP basis was $326.5 million and $413.8 million, respectively.

Adjusted EBITDA: Third-quarter 2021 adjusted EBITDA was $509.0 million.

Earnings per Share: On a GAAP basis, diluted earnings per share in the third quarter of 2021 and 2020 were $1.38 and $1.31, respectively. Non-GAAP diluted earnings per share in the third quarter of 2021 and 2020 were $1.75 and $1.74, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the third quarter of 2021 were 236.2 million.
Third-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments, the orphan segment and the inflammation segment. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results.

Third-quarter 2021 net sales of the orphan segment, the Company’s strategic growth segment, were $951.0 million, an increase of 78 percent over the prior year’s quarter, driven by the strong performance of TEPEZZA, KRYSTEXXA, RAVICTI, PROCYSBI and ACTIMMUNE. The orphan segment represented 92 percent of total company third-quarter net sales.

KRYSTEXXA third-quarter 2021 net sales increased 46 percent year-over-year driven by increased adoption of KRYSTEXXA plus immunomodulation, which now exceeds 45 percent. In addition, the Company continues to see strong uptake of KRYSTEXXA from both rheumatologists and nephrologists.

Third-quarter 2021 orphan segment operating income was $476.2 million, which includes additional investment associated with TEPEZZA, UPLIZNA and the Company’s pipeline programs.
Third-quarter 2021 net sales of the inflammation segment were $86.0 million, and segment operating income was $34.1 million.
Cash Flow Statement and Balance Sheet Highlights

On a GAAP basis, operating cash flow in the third quarter of 2021 was $411.0 million. Non-GAAP operating cash flow was $432.3 million.
As of Sept. 30, 2021, the Company had cash and cash equivalents of $1.069 billion.
As of Sept. 30, 2021, the total principal amount of debt outstanding was $2.610 billion, and the gross-debt-to-last-12-months adjusted EBITDA leverage ratio was 2.0 times.
2021 Guidance

The Company now expects full‐year 2021 net sales to range between $3.16 billion and $3.21 billion, representing 45 percent growth at the midpoint and an increase from the previous range of $3.025 billion to $3.125 billion. The company now expects TEPEZZA full-year 2021 net sales of greater than $1.625 billion with year-over-year growth of more than 60 percent in the fourth quarter, compared to the previous guidance of greater than $1.550 billion with year-over-year growth of more than 50 percent in the fourth quarter. The Company now expects KRYSTEXXA full-year 2021 net sales of greater than $550 million, compared to the previous guidance of greater than $500 million. Full-year 2021 adjusted EBITDA is now expected to range between $1.315 billion and $1.345 billion, representing 33 percent growth at the midpoint and an increase from the previous guidance range of $1.26 billion to $1.30 billion.

Webcast

At 8 a.m. EST / 12 p.m. GMT today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.

On November 3, 2021 ITM Isotope Technologies Munich SE reported the presentation of the design of its new phase III trial, COMPOSE, with the radiopharmaceutical candidate n.c.a. 177Lu-edotreotide in patients with well‐differentiated aggressive grade 2 and grade 3 somatostatin receptor-positive gastro-enteropancreatic neuroendocrine tumors (GEP-NETs) at the North American Neuroendocrine Society (NANETS) annual symposium 2021, held virtually from November 3 – 6, 2021 (Press release, ITM Isotopen Technologien Munchen, NOV 3, 2021, View Source [SID1234594269]). COMPOSE is ITM’s second phase III trial with its lead candidate n.c.a. 177Lu-edotreotide, a Targeted Radionuclide Therapy consisting of the high-quality radioisotope no-carrier-added lutetium-177 fused with an innovative somatostatin analogue to specifically target GEP-NETs. N.c.a. 177Lu-edotreotide is also currently being investigated in an ongoing phase III study, COMPETE, in patients with grade 1 and 2 GEP-NETs.

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"The most common form of NETs is gastroenteropancreatic and often develops metastatic disease, limiting treatment options. N.c.a. 177Lu-edotreotide has previously shown a favorable safety and efficacy profile in GEP-NETs and with COMPOSE we aim to also make it available to late-stage patients suffering from this hard-to-treat cancer indication," stated Steffen Schuster, CEO of ITM. "We look forward to the opportunity of introducing our phase III COMPOSE trial to the global scientific community at the NANETS symposium, a key oncology event that features leading research, education, and emerging practices on NETs."

COMPOSE (NCT04919226) is an international, prospective, randomized, controlled, open-label, multi-center phase III study to evaluate the efficacy, safety, and patient-reported outcomes of first or second-line treatment with n.c.a. 177Lu-edotreotide PRRT compared to best standard of care in patients with well-differentiated aggressive grade 2 and grade 3 (Ki-67 index 15-55), somatostatin receptor-positive (SSTR+), GEP-NETs. The study aims to randomize 202 patients 1:1 to n.c.a. 177Lu-edotreotide or to an active comparator — either chemotherapy (CAPTEM or FOLFOX) or everolimus — according to the investigator’s choice. The primary endpoint of the study is progression-free survival (PFS), which will be assessed every 12 weeks from randomization onwards. Secondary outcome measures include overall survival (OS) up to two years after disease progression.

Presentation information

Title: COMPOSE: Pivotal phase III trial of 177Lu-edotreotide versus best standard of care in well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors
Abstract No: 136
Poster No: 410
Session: Phase III Clinical Trials in Progress
Presenter: Prof. Thorvardur Halfdanarson, Mayo Clinic, Rochester, MN, USA

For more information on COMPOSE and ITM, visit the ITM virtual booth at the NANETS virtual industry exhibition.

– End –

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing radiation exposure to normal tissue. Targeted radiopharmaceuticals are created by linking a therapeutic radioisotope to a targeting molecule (e.g., peptide, antibody, small molecule) that can precisely recognize tumor cells and bind to tumor-specific characteristics, like receptors on the tumor cell surface. As a result, the radioisotope accumulates at the tumor site and decays, releasing a small amount of ionizing radiation, thereby destroying the tumor. The highly precise localization enables targeted treatment with minimal impact to healthy surrounding tissue.

About n.c.a. 177Lu-edotreotide

N.c.a. 177Lu-edotreotide is ITM’s therapeutic radiopharmaceutical candidate being investigated in the phase III clinical studies COMPETE and COMPOSE and consists of two components: the medical radioisotope no-carrier-added lutetium-177 (n.c.a. 177Lu) and the targeting molecule edotreotide, a synthetic form of the peptide hormone somatostatin that targets neuroendocrine tumor-specific receptors. Edotreotide binds to these receptors and places the medical radioisotope n.c.a. lutetium-177 directly onto the diseased neuroendocrine cells so that it accumulates at the tumor site. N.c.a. lutetium-177 is internalized into the tumor cells and decays, releasing medical radiation (ionizing β-radiation) with a maximum radius of 1.7 mm and destroying the tumor. The highly precise localization can result in the healthy tissue surrounding the targeted tumor being minimally affected.

On November 3, 2021 Memgen, Inc. reported that the U.S. Food and Drug Administration (FDA) has accepted its investigational new drug (IND) application for MEM-288, the company’s wholly-owned cancer immunotherapy candidate for the treatment of multiple solid tumors (Press release, Memgen, NOV 3, 2021, View Source [SID1234594268]). Memgen intends to initiate screening of patients by year-end in a Phase 1 first-in-human study.

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"The FDA’s acceptance of our IND for MEM-288 is an important milestone in our pursuit of developing life-saving cancer immunotherapies in collaboration with leading cancer centers including the Moffitt Cancer Center and the Duke Cancer Institute," said Mark Cantwell, Ph.D., Chief Scientific Officer of Memgen. "We expect to initiate this first-in-human study in patients with non-small cell lung cancer, as well as those with other types of cancer, by year-end."

Memgen’s Phase 1 trial is an open-label, dose escalation study designed to evaluate the safety, tolerability, biologic activity and anti-tumor effects of MEM-288. In addition to non-small cell lung cancer (NSCLC), the trial may enroll patients with triple-negative breast cancer, pancreatic cancer, head and neck cancer, melanoma, cutaneous squamous-cell carcinoma, and Merkel cell carcinoma. Except for patients with pancreatic cancer, these are patients whose disease has progressed following treatment with anti-PD-1/PD-L1 therapy, and who have tumor lesions accessible for injection.

Duke Cancer Institute and the H. Lee Moffitt Cancer will be the initial clinical trial sites. Memgen expects patient recruitment to begin by December 31, 2021. Additional information about the study, including patient inclusion and exclusion criteria, can be found at ClinicalTrials.gov under study identifier NCT05076760.

The study will evaluate the oncolytic effect of MEM-288 as well as the activation of the patients’ immune system including T-cells. While the focus of the initial Phase 1 study will be patients with NSCLC, MEM-288 has shown robust anti-tumor effects in 13 different types of cancer. Once safety and tolerability have been evaluated in this trial, Memgen plans to expand clinical development of MEM-288 across multiple cancers and in combination with an immune checkpoint inhibitor.

About MEM-288
MEM-288 is an oncolytic adenovirus encoding transgenes for human interferon beta (IFNß) and the company’s proprietary recombinant chimeric CD40 ligand. MEM-288, armed with Memgen’s proprietary CD40 ligand, leverages a validated target that powerfully activates the patient’s immune system. The company’s proprietary CD40 ligand has been evaluated in earlier clinical studies and demonstrated significant immune activation without the toxicity that had previously prevented development of safe CD40-based therapeutics. Because the CD40 system works as a master "on switch" for the immune system upstream from the immune checkpoint inhibitors, it holds promise in those patients whose disease has progressed despite treatment with immune checkpoint inhibitors.

On November 3, 2021 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported that due to supply-chain issues affecting its drug-supply manufacturer, the start date of its two upcoming NOX-A12 clinical trials will be delayed by up to 3 months until Q3 2022 (Press release, NOXXON, NOV 3, 2021, View Source [SID1234594267]). The affected trials are the Phase 2 trial (OPTIMUS) with NOX-A12 in combination with MSD’s (Merck & Co., Inc., Kenilworth, N.J. USA) anti-PD-1 therapy Keytruda (pembrolizumab) as second-line therapy in pancreatic cancer, and the planned pivotal Phase 2/3 trial of NOX-A12 in combination with radiotherapy in first-line brain cancer (glioblastoma) patients.

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Due to a shortage in the US of dichloroacetic acid, a key chemical reagent necessary to synthesize NOX-A12, NOXXON has been informed by its contract active ingredient manufacturer that the NOX-A12 batches needed to initiate these two studies will only be available in Q2 2022 with first patients therefore expected to be dosed in early August 2022. These delays have impacted the overall approval timelines of NOX-A12 in glioblastoma, pushing it into early 2026, while market approval in pancreatic cancer remains unchanged and is planned in 2027.

Aram Mangasarian, CEO of NOXXON commented: "The effects of the COVID-19 pandemic continue to impact the healthcare industry in many areas, including the most essential ones like manufacturing supply chains. The NOX-A12 studies in pancreatic and brain cancer are our key clinical programs; the pancreas cancer trial is our second collaboration with MSD, a global leader in the immuno-oncology space, and the pivotal brain cancer trial is expected to deliver the data base for our first marketing authorization. We have worked with our contract manufacturer to overcome the unexpected shortages of what are usually easily sourced chemical reagents affecting these batches of NOX-A12 and are doing everything to ensure these batches will be released as soon as possible with the usual high standards of quality. We look forward to getting the trials underway and examining the potential clinical benefits of NOX-A12 in combination with Keytruda or radiotherapy for patients suffering from highly aggressive cancers."

With €13.7 million in cash and cash equivalents on June 30, 2021 and available secured financing of €10.45 million (nominal) drawable at the company’s discretion as reported on October 22, 2021 with the Half-Year Financial Report 2021, updated timing of commitments for manufacturing and clinical trials extends NOXXON’s financial visibility into July 2022.