On November 6, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, reported financial results for the third quarter ended September 30, 2024, and provided a pipeline update on its clinical-stage investigational molecules – targeting TIGIT, HIF-2a, CD73, the A2a/A2b receptors, CD-39, AXL and PD-1 – across multiple common cancers (Press release, Arcus Biosciences, NOV 6, 2024, View Source [SID1234647801]).

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"Through the course of this year, we have presented multiple compelling datasets at medical conferences that we believe have de-risked several programs and support potential best-in-class profiles for our molecules, including our HIF-2a inhibitor casdatifan in ccRCC and our Fc-silent anti-TIGIT antibody domvanalimab in lung and upper gastrointestinal cancers," said Terry Rosen, Ph.D., chief executive officer of Arcus. "Meanwhile, in addition to our rapidly approaching first Phase 3 readout for domvanalimab in gastric cancer, we are aggressively pursuing our development plan for casdatifan, including in the IO-naive ccRCC setting in collaboration with AstraZeneca, and in the post-IO setting with the initiation of our Phase 3 PEAK-1 study in the first half of next year."
Corporate Updates:

•In October 2024, Arcus announced a clinical collaboration with AstraZeneca to evaluate casdatifan in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in IO-naive patients with ccRCC. AstraZeneca will operationalize the study. This is the second clinical collaboration between Arcus and AstraZeneca. Gilead retains the right to opt in to the development and commercialization for casdatifan after delivery of a qualifying data package.
Pipeline Highlights:

Casdatifan (HIF-2a inhibitor)
Casdatifan Updates:
•First clinical data from the casdatifan 100mg and 50mg expansion cohorts of ARC-20, a Phase 1/1b study in metastatic ccRCC, were presented in an oral plenary session at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October. Observations from the 100mg daily expansion cohort included:
◦An objective response rate (ORR) of 34% (2 responses are pending confirmation; 25% confirmed ORR), a low rate of primary progression of 19% and a high disease control rate of 81%.
◦The median progression-free survival (PFS) had not been reached at the time of the data cutoff.

◦Together, these data support the potential for casdatifan to be a best-in-class HIF-2a inhibitor for the treatment of ccRCC.
•In the third quarter, Arcus had a successful Type B meeting with the U.S. Federal Drug Administration (FDA) to discuss its first Phase 3 study for casdatifan, PEAK-1, which will evaluate casdatifan in combination with cabozantinib versus cabozantinib in post-IO patients with ccRCC. Arcus is moving rapidly toward the initiation of PEAK-1 in the first half of 2025.
Upcoming Casdatifan Milestones:
•Multiple expansion cohorts of ARC-20 evaluating casdatifan in ccRCC as a monotherapy and in combination with cabozantinib in ccRCC are underway with additional data presentations expected in the next 12 months.
◦100mg (50mg twice daily (BID), capsules) and 50mg expansion cohorts: Updated data, including median PFS, are expected to be presented in the first quarter of 2025.
◦150mg and 100mg (once daily (QD), tablets) expansion cohorts: Initial data are expected to be presented in 2025.
◦100mg of casdatifan plus cabozantinib: Safety data are expected to be presented in 2025.
Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody)
Domvanalimab-Zimberelimab Updates:
•Data from Part 1 of ARC-10, a randomized study evaluating domvanalimab plus zimberelimab in PD-L-1 high NSCLC are being presented at the SITC (Free SITC Whitepaper) Annual Meeting in November.
•Domvanalimab plus zimberelimab was associated with greater PFS, overall survival, and objective response rate compared with zimberelimab or chemotherapy.
◦A 36% reduction in risk of death (hazard ratio [HR]=0.64) was observed for domvanalimab plus zimberelimab compared to that of zimberelimab alone.
◦Zimberelimab reached a median overall survival of 2 years, and the median overall survival for domvanalimab plus zimberelimab was not reached.
◦Treatment-related adverse events leading to treatment discontinuation were low (10.5%) for the combination of domvanalimab and zimberelimab.
•Data from an investigator-sponsored trial evaluating domvanalimab plus zimberelimab in anti-PD-(L)1 refractory hepatocellular carcinoma will be presented in an oral session at the SITC (Free SITC Whitepaper) Annual Meeting.
Upcoming Domvanalimab-Zimberelimab Milestones:
•Overall survival data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper gastrointestinal (GI) adenocarcinomas, are expected to be presented in 2025.

CD73-Adenosine Axis: Quemliclustat (small-molecule CD73 inhibitor) and Etrumadenant (A2a/A2b receptor antagonist)

Quemliclustat
•Arcus has initiated PRISM-1, a Phase 3 trial of quemliclustat combined with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in pancreatic cancer.
Etrumadenant
•Biomarker data from cohort B of ARC-9, a randomized Phase 1b/2 study evaluating etrumadenant plus zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) versus regorafenib in third-line metastatic colorectal cancer (mCRC), are being presented at SITC (Free SITC Whitepaper) in November.

Early Clinical Programs

•Evaluation of AB801, a potent and highly selective small-molecule AXL inhibitor, in the dose-escalation phase of a Phase 1/1b study in patients is ongoing. Arcus anticipates advancing this molecule into expansion cohorts in NSCLC in early 2025.
Financial Results for Third Quarter 2024:
•Cash, Cash Equivalents and Marketable Securities were $1.1 billion as of September 30, 2024, compared to $866 million as of December 31, 2023. The increase during the period is primarily due to the receipt of $320 million in cash from Gilead for their January 2024 equity investment, the receipt of the $100 million option continuation payment from Gilead in July 2024 and proceeds from our $50 million term loan, partially offset by the use of cash in research and development activities. We believe our cash, cash equivalents and marketable securities on-hand will be sufficient to fund operations into mid-2027. Cash, cash equivalents and marketable securities are expected to be between $950 million and $985 million at the end of 2024.
•Revenues were $48 million for the third quarter 2024, compared to $32 million for the same period in 2023. In the third quarter 2024, Arcus recognized $41 million in license and development services revenue related to the advancement of programs and Taiho’s exercise of its option for the license of quemliclustat for the Taiho Territory of $15 million, as well as $7 million in other collaboration revenue primarily related to Gilead’s ongoing rights to access Arcus’s research and development pipeline in accordance with the Gilead collaboration agreement.
•Research and Development (R&D) Expenses were $123 million for the third quarter 2024, compared to $82 million for the same period in 2023. The net increase of $41 million was primarily driven by higher clinical trial and headcount-related costs associated with our late-stage development program activities. Non-cash stock-based compensation expense was $9 million for the third quarter 2024, compared to $8 million for the same period in 2023. For the third quarter 2024 and 2023, Arcus recognized gross reimbursements of $37 million and $33 million, respectively, for shared expenses from its collaborations, primarily the Gilead collaboration. R&D expense by quarter may fluctuate due to the timing of clinical manufacturing and standard-of-care therapeutic purchases with a corresponding impact on reimbursements.
•General and Administrative (G&A) Expenses were flat for the third quarter 2024, compared to the same period in 2023. Non-cash stock-based compensation expense was $10 million for each of the third quarter 2024 and 2023.
•Net Loss was $92 million for the third quarter 2024, compared to $71 million for the same period in 2023.
Conference Call Information:
Arcus will host a conference call and webcast today, November 6, at 2:00 PM PT / 5:00 PM ET to discuss its third-quarter 2024 financial results and pipeline updates. To access the call, please dial +1 (404) 975-4839 (local) or +1 (833) 470-1428 (toll-free), using Access Code: 940081. Participants may also register for the call online using the following link: View Source;confId=72838. To access the live webcast and accompanying slide presentation, please visit the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay of the webcast will be available following the live event.
Arcus Ongoing and Announced Clinical Studies:
Trial Name Arms Setting Status NCT No.
Lung Cancer
STAR-121 dom + zim + chemo vs. pembro + chemo 1L NSCLC (PD-L1 all-comers) Ongoing Registrational Phase 3
NCT05502237
PACIFIC-8 dom + durva vs. durva Unresectable Stage 3 NSCLC Ongoing Registrational Phase 3
NCT05211895
ARC-7 zim vs. dom + zim vs. etruma + dom + zim 1L NSCLC (PD-L1 ≥ 50%) Ongoing Randomized Phase 2
NCT04262856
EDGE-Lung dom +/- zim +/- quemli +/- chemo 1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2
NCT05676931
VELOCITY-Lung
dom +/- zim +/- etruma +/- sacituzumab govitecan-hziy or other combos
1L/2L NSCLC (lung cancer platform study) Ongoing Randomized Phase 2
NCT05633667
Upper Gastrointestinal Cancers
STAR-221 dom + zim + chemo vs. nivo + chemo 1L Gastric, GEJ and EAC Ongoing Registrational Phase 3
NCT05568095
EDGE-Gastric (ARC-21) dom +/- zim +/- quemli +/- chemo 1L/2L Upper GI Malignancies
Ongoing
Randomized Phase 2
NCT05329766
Colorectal Cancer

ARC-9 etruma + zim + mFOLFOX vs. SOC 2L/3L/3L+ CRC
Ongoing
Randomized Phase 2
NCT04660812
Pancreatic Cancer
PRISM-1 quemli + gem/nab-pac vs. gem/nab-pac 1L PDAC Ongoing Phase 3
NCT06608927
ARC-8 quemli + zim + gem/nab-pac vs. quemli + gem/nab-pac 1L, 2L PDAC Ongoing Randomized Phase 1/1b
NCT04104672
Kidney Cancer
PEAK-1 cas + cabo vs. cabo Post-IO ccRCC Planned Phase 3 TBD
ARC-20 cas, cas + cabo Cancer Patients / ccRCC Ongoing Phase 1/1b
NCT05536141
Other
ARC-25 AB598 Advanced Malignancies Ongoing
NCT05891171
ARC-27 AB801 Advanced Malignancies Ongoing
NCT06120075

cabo: cabozantinib; cas: casdatifan; dom: domvanalimab; durva: durvalumab; etruma: etrumadenant; gem/nab-pac: gemcitabine/nab-paclitaxel; nivo: nivolumab; pembro: pembrolizumab; quemli: quemliclustat; SOC: standard of care; zim: zimberelimab; ccRCC: clear cell renal cell carcinoma; CRC: colorectal cancer; EAC: esophageal adenocarcinoma; GEJ: gastroesophageal junction; GI: gastrointestinal; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma.

On November 6, 2024 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported its financial results for the third quarter ended September 30, 2024 and provided a business update (Press release, Immunocore, NOV 6, 2024, View Source [SID1234647817]).

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"We are proud to report another strong quarter, marking two years of continuous growth for KIMMTRAK and another quarter of positive net income," said Bahija Jallal, Immunocore’s Chief Executive Officer. "We are also making significant strides in advancing our broad pipeline – with brenetafusp in oncology, the HIV functional cure trial in infectious diseases, and in autoimmune diseases with tissue-targeted programs for type 1 diabetes and dermatologic diseases."

"KIMMTRAK’s 28% growth over Q3 last year is driven by higher demand in the United States and Germany and by expanded patient reach with 11 launches this year," said Ralph Torbay, Immunocore’s Chief Commercial Officer. "We are excited about the potential to bring KIMMTRAK to more patients with melanoma through the Phase 3 TEBE-AM trial that is expected to complete enrollment in early 2026, and the Phase 3 ATOM trial that is planned to start randomization this quarter."

Third Quarter 2024 Highlights (including post-period)

KIMMTRAK
The Company’s lead product, KIMMTRAK, is approved in 38 countries and has been launched in 21 countries globally to date for HLA-A*02:01 positive patients with unresectable or metastatic uveal melanoma (mUM). KIMMTRAK continues to be the standard of care in most markets where it is launched. The Company sees three key growth areas for KIMMTRAK: continued expansion in mUM, the potential expansion into 2L+ advanced cutaneous melanoma and adjuvant uveal melanoma.

Metastatic uveal melanoma

KIMMTRAK net product sales were $80.2 million and $225.9 million for the three and nine months ended September 30, 2024, respectively, representing increases of 28% and 32% respectively, compared to the prior year periods.
Growth in the US and Germany was driven by increased demand based on continued community penetration and growing duration of treatment.
New baseline blood gene expression signature data was presented at the European Society for Medical Oncology 2024 Meeting (ESMO 2024) confirming that T cell fitness in blood is an important parameter of clinical activity for KIMMTRAK in previously treated uveal melanoma.

2L+ previously treated cutaneous melanoma

Randomization continues in the registrational Phase 3 trial (TEBE-AM), which includes three arms – KIMMTRAK monotherapy, KIMMTRAK in combination with pembrolizumab, and control. The Company expects to complete randomization in the first half of 2026.
The TEBE-AM Phase 3 trial in 2L+ cutaneous melanoma has a primary endpoint of overall survival.
Adjuvant uveal (or ocular) melanoma

Randomization in the ATOM Phase 3 trial, led by the European Organisation for Research and Treatment of Cancer (EORTC), is on track to start in the fourth quarter of 2024.
ATOM is currently the only active registrational Phase 3 trial in adjuvant uveal melanoma.
PRAME
Brenetafusp (IMC-F106C) is the Company’s lead PRAME-A02 ImmTAC bispecific candidate. Brenetafusp is being evaluated in combination with nivolumab, in a Phase 3 registrational trial (PRISM-MEL-301) in patients with first-line advanced cutaneous melanoma and in a Phase 1/2 clinical trial, as monotherapy and in combination, across multiple tumor types, including ovarian, non-small cell lung (NSCLC), and endometrial carcinoma.

PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced or metastatic HLA-A*02:01 positive cutaneous melanoma

Ongoing randomization of patients in PRISM-MEL-301 in multiple countries.
Trial is evaluating brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab.
Phase 1/2 clinical trial of brenetafusp (PRAME-A02) in multiple solid tumors

Clinical data presented at ESMO (Free ESMO Whitepaper) 2024 from the Phase 1 trial in patients with heavily pre-treated platinum-resistant high grade serous ovarian cancer showed signals of activity in heavily pretreated, platinum resistant patients. Disease control rate was 58% in monotherapy patients and 69% for combination patients. Overall survival (OS) was still maturing (73% 6-months OS rate in the monotherapy cohort). ctDNA molecular response rate was 31% and 82%, respectively, in the monotherapy and combination cohorts, associated with longer progression free survival and OS. Brenetafusp is well tolerated as monotherapy and in combination with gemcitabine, nab-paclitaxel and pegylated doxorubicin.
Data presented at ESMO (Free ESMO Whitepaper) 2024 showed peripheral blood T cell fitness signature is an important parameter of brenetafusp clinical activity in ovarian cancer and uveal melanoma.
The Company is currently evaluating brenetafusp in combination with non-platinum chemotherapies in platinum resistant ovarian cancer and with bevacizumab and with platinum chemotherapy in earlier lines of platinum sensitive ovarian cancer.
The Company continues signal detection for brenetafusp in metastatic non-small-cell lung cancer cohorts, including in combination with docetaxel and with osimertinib in earlier-line NSCLC. As a result, the Company will not release initial data in the fourth quarter of 2024.
IMC-P115C (PRAME-A02 Half-Life Extended) & IMC-T119C (PRAME-A24)

On track for first patient to be treated in the Phase 1 trial with IMC-P115C in first half of 2025.

Additional Oncology Candidates

IMC-R117C (first PIWIL1-A02 targeted immunotherapy) for colorectal and other gastrointestinal cancers
The Company has leveraged its proprietary peptidomic database to validate a novel target, PIWIL1. PIWIL1 is a negative prognostic marker and is expressed across a range of tumors including colorectal, which is historically insensitive to immune checkpoints, as well as gastro-esophageal, and pancreatic cancer.

Remain on track to treat the first patient in the Phase 1/2 trial of IMC-R117C in the fourth quarter of 2024.
The Phase 1/2 trial will assess the safety and clinical activity of IMC-R117C, as a monotherapy and in combination with standards of care, in colorectal and other gastrointestinal cancers.
ImmTAV candidates for a functional cure in infectious diseases
The Company’s bispecific TCR technology platform has potential to offer a new approach for the treatment of chronic infections and aims to eliminate evidence of remaining virus in circulation after the patient stops taking medication – known as a "functional cure". Two investigational candidates are in Phase 1 clinical trials for people living with human immunodeficiency virus (HIV) and people with chronic Hepatitis B infection (HBV).

Phase 1 trial of IMC-M113V (Gag-A02) for people living with HIV

The objective of the clinical trial is to identify a safe and tolerable dose and evaluate whether IMC-M113V could lead to reduction in the viral reservoir and, after stopping antiretroviral therapies and IMC-M113V, delay or prevent HIV rebound.
A biologically active dose in the multiple ascending dose (MAD) portion of the trial has been reached and the Company is enrolling more people living with HIV to characterize anti-viral activity and to explore higher doses with data expected in the first quarter of 2025.
Phase 1 trial of IMC-I109V (Envelope-A02) for people living with HBV

Expect to complete the single ascending dose (SAD) portion of the trial in the fourth quarter of 2024.

Tissue-specific down modulation of the immune system for autoimmune diseases
The Company is expanding its platform into autoimmune diseases with two new, first-in-class bispecific candidates recently entering its pipeline. The key differentiator of the Company’s ImmTAAI (Immune Modulating Monoclonal TCRs Against AutoImmune disease) platform is tissue-specific down modulation of the immune system whereby, when tethered to the tissue of interest, the new candidates suppress pathogenic T cells via PD1 receptor agonism.

IMC-S118AI (pre-pro insulin A02 x PD1), intended for disease-modifying treatment in type 1 diabetes

IMC-S118AI recognizes a peptide from pre-proinsulin presented by HLA-A02 on beta cells, coupled with a PD1 agonist effector arm.

Undisclosed non-HLA restricted (universal) candidate for inflammatory dermatological diseases

The candidate is an antigen presenting cell (APC) tethered ImmTAAI and is not HLA restricted (i.e. universal for all populations).

Corporate Updates

In August, Chief Financial Officer (CFO) and Head of Strategy, Brian Di Donato, informed the Company of his plans to leave at the end of the year, to take the role of Chief Executive Officer at a private, early-stage biotech headquartered in San Diego, California. The Company is progressing in its search for a new CFO. Brian will remain as the Company’s CFO and Head of Strategy through the end of 2024, to ensure a smooth transition.

Financial Results

For the third quarter ended September 30, 2024, the Company generated net product sales of $80.2 million compared to $62.6 million for the same period in 2023. This increase was due to revenue from KIMMTRAK, of which $57.3 million was in the United States, $21.0 million in Europe, and $1.9 million in international regions. The increase in net product sales was due primarily to increased volume in the United States and global country expansion, as the Company continued its commercialization efforts.

For the third quarter ended September 30, 2024, research and development (R&D) expenses were $52.8 million, compared to $43.2 million for the same period in 2023. This increase was primarily driven by expenses incurred for the tebentafusp programs, including the Phase 3 trials: TEBE-AM in previously treated advanced cutaneous melanoma and ATOM in adjuvant uveal melanoma.

For the quarter ended September 30, 2024, SG&A expenses were $35.5 million, compared to $35.5 million for the same period in 2023.

Basic and diluted earnings per share was $0.17 for the quarter ended September 30, 2024, as compared to a basic and diluted earnings per share of $0.02 for the same period in 2023. Net income for the quarter ended September 30, 2024 was $8.7 million, as compared to $0.9 million for the same period in 2023.

Cash, cash equivalents, and marketable securities at September 30, 2024 were $901.3 million. The Company plans to use existing cash to repay its $50 million loan by the end of 2024 and also expects to pay approximately $40 million in sales-related rebate accruals in the fourth quarter of 2024.

About ImmTAC molecules for cancer

Immunocore’s proprietary T cell receptor (TCR) technology generates a novel class of bispecific biologics called ImmTAC (Immune mobilizing monoclonal TCRs Against Cancer) molecules that are designed to redirect the immune system to recognize and kill cancerous cells. ImmTAC molecules are soluble TCRs engineered to recognize intracellular cancer antigens with ultra-high affinity and selectively kill these cancer cells via an anti-CD3 immune-activating effector function. Based on the demonstrated mechanism of T cell infiltration into human tumors, the ImmTAC mechanism of action holds the potential to treat hematologic and solid tumors, regardless of mutational burden or immune infiltration, including immune "cold" low mutation rate tumors.

About ImmTAV molecules and infectious diseases

ImmTAV (Immune mobilizing monoclonal TCRs Against Virus) molecules are novel bispecifics that are designed to enable the immune system to recognize and eliminate virally infected cells.
Immunocore is advancing clinical candidates to achieve functional cure for patients with HIV and hepatitis B virus (HBV). The Company aims to achieve sustained control of HIV after patients stop anti-retroviral therapy (ART), without the risk of virological relapse or onward transmission. This is known as ‘functional cure’. For the treatment of HBV, the Company aims to achieve sustained loss of circulating viral antigens and markers of viral replication after stopping medication for people living with chronic HBV.

About ImmTAAITM molecules and autoimmune diseases

ImmTAAI (Immune mobilizing monoclonal TCRs Against AutoImmune disease) molecules are novel bispecifics that are designed for tissue-specific down modulation of the immune system. When tethered to the tissue of interest, ImmTAAI candidates suppress pathogenic T cells via PD1 receptor agonism. The Company is currently advancing two candidates for autoimmune diseases, including type 1 diabetes and inflammatory dermatological diseases.

About PRISM-MEL-301 (NCT06112314) – Phase 3 trial with brenetafusp (IMC-F106C, PRAME-A02) in 1L advanced cutaneous melanoma

The Phase 3 registrational trial is randomizing HLA-A*02:01-positive patients with previously untreated advanced melanoma, to brenetafusp + nivolumab versus nivolumab or nivolumab + relatlimab, depending on the country where the patient is enrolled. The trial will initially randomize to three arms: two brenetafusp dose regimens (40 mcg and 160 mcg) and a control arm. One of the two brenetafusp dose regimens will be discontinued after an initial review of the first 60 patients randomized to the two experimental arms (90 patients randomized total). The primary endpoint of the trial is progression free survival (PFS) by blinded independent central review (BICR), with secondary endpoints of overall survival (OS) and overall response rate (ORR).

About the IMC-F106C-101 Phase 1/2 trial

IMC-F106C-101 is a first-in-human, Phase 1/2 dose escalation trial in patients with multiple solid tumors, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), endometrial, ovarian, cutaneous melanoma, and breast cancers. The Phase 1 dose escalation trial was designed to determine the maximum tolerated dose (MTD), as well as to evaluate the safety, preliminary anti-tumor activity and pharmacokinetics of IMC-F106C (brenetafusp), a bispecific protein built on Immunocore’s ImmTAC technology, and the Company’s first molecule to target the PRAME antigen. The Company is enrolling patients into three expansion arms in NSCLC, as well as ovarian and endometrial carcinomas. The IMC-F106C-101 trial is adaptive and includes the option for Phase 2 expansion, allowing for approximately 100 patients treated per tumor type in the Phase 1 and 2 expansion arms. Dose escalation continues in additional solid tumors as well as plans for combination arms with standards-of-care, including checkpoint inhibitors, chemotherapy, and tebentafusp.

About TEBE-AM – Phase 3 registrational trial with tebentafusp in previously treated advanced cutaneous melanoma

The trial is randomizing patients with second-line or later advanced cutaneous melanoma who have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a BRAF kinase inhibitor. Patients are randomized to one of three arms, including tebentafusp – as monotherapy or in combination with an anti-PD1 – or a control arm. The primary endpoint is overall survival.

About the ATOM Phase 3 trial – Phase 3 registrational trial with tebentafusp in adjuvant uveal melanoma

The EORTC-led Phase 3 clinical trial will include sites in 10 EU countries and the United States and will randomize HLA-A*02:01-positive patients with high-risk primary uveal melanoma after definitive treatment, by surgery or radiotherapy, and no evidence of metastatic disease on imaging. The trial is expected to enroll a total of 290 patients who will be randomized 1:1 to one of two arms: tebentafusp as monotherapy or observation. The primary endpoint of the trial is relapse-free survival (RFS), with secondary objectives of overall survival and safety and tolerability of tebentafusp. Exploratory objectives include comparison of health-related quality of life between the treatment arms and evaluation of the role of circulating tumor DNA (ctDNA) as a biomarker for the presence of residual disease.

About Uveal Melanoma

Uveal melanoma is a rare and aggressive form of melanoma affecting the eye. Although it is the most common primary intraocular malignancy in adults, the diagnosis is rare, and up to 50% of people with uveal melanoma will eventually develop metastatic disease. Unresectable or metastatic uveal melanoma typically has a poor prognosis and had no approved treatment until KIMMTRAK.

About Cutaneous Melanoma

Cutaneous melanoma (CM) is the most common form of melanoma. It is the most aggressive skin carcinoma and is associated with the vast majority of skin cancer-related mortality. The majority of patients with CM are diagnosed before metastasis but survival remains poor for the large proportion of patients with metastatic disease. Despite recent progress in advanced melanoma therapy, there is still an unmet need for new therapies that improve first-line response rates and duration of response as well as for patients who are refractory to first-line treatments.

About KIMMTRAK

KIMMTRAK is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector function. KIMMTRAK specifically targets gp100, a lineage antigen expressed in melanocytes and melanoma. This is the first molecule developed using Immunocore’s ImmTAC technology platform, designed to redirect and activate T cells to recognize and kill tumor cells. KIMMTRAK has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma in the United States, European Union, Canada, Australia, and the United Kingdom.

IMPORTANT SAFETY INFORMATION

Cytokine Release Syndrome (CRS), which may be serious or life-threatening, occurred in patients receiving KIMMTRAK. Monitor for at least 16 hours following first three infusions and then as clinically indicated. Manifestations of CRS may include fever, hypotension, hypoxia, chills, nausea, vomiting, rash, elevated transaminases, fatigue, and headache. CRS occurred in 89% of patients who received KIMMTRAK, with 0.8% being grade 3 or 4. Ensure immediate access to medications and resuscitative equipment to manage CRS. Ensure patients are euvolemic prior to initiating the infusions. Closely monitor patients for signs or symptoms of CRS following infusions of KIMMTRAK. Monitor fluid status, vital signs, and oxygenation level and provide appropriate therapy. Withhold or discontinue KIMMTRAK depending on persistence and severity of CRS.

Skin Reactions

Skin reactions, including rash, pruritus, and cutaneous edema occurred in 91% of patients treated with KIMMTRAK. Monitor patients for skin reactions. If skin reactions occur, treat with antihistamine and topical or systemic steroids based on persistence and severity of symptoms. Withhold or permanently discontinue KIMMTRAK depending on the severity of skin reactions.

Elevated Liver Enzymes

Elevations in liver enzymes occurred in 65% of patients treated with KIMMTRAK. Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total blood bilirubin prior to the start of and during treatment with KIMMTRAK. Withhold KIMMTRAK according to severity.

Embryo-Fetal Toxicity

KIMMTRAK may cause fetal harm. Advise pregnant patients of potential risk to the fetus and patients of reproductive potential to use effective contraception during treatment with KIMMTRAK and 1 week after the last dose.

The most common adverse reactions (≥30%) in patients who received KIMMTRAK were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common (≥50%) laboratory abnormalities were decreased lymphocyte count, increased creatinine, increased glucose, increased AST, increased ALT, decreased hemoglobin, and decreased phosphate.

For more information, please see full Summary of Product Characteristics (SmPC) or full U.S. Prescribing Information (including BOXED WARNING for CRS).

On November 5, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported financial results for the third quarter ended September 30, 2024, and provided an overview of recent developments (Press release, UroGen Pharma, NOV 6, 2024, View Source [SID1234647833]).

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Discover why more than 1,500 members use 1stOncology™ to excel in:

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"The recent FDA acceptance of our New Drug Application for UGN-102 marks a significant milestone in our mission to deliver breakthrough treatments to patients," said Liz Barrett, President and Chief Executive Officer of UroGen. "Supported by robust clinical evidence, we believe UGN-102 has the potential to redefine the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer and provide longer treatment-free intervals for patients that currently face the burden of repetitive surgeries under general anesthesia. We look forward to a potential FDA approval by the PDUFA target action date of June 13, 2025. If approved, we believe UGN-102 will represent a paradigm shift in care, addressing a total market opportunity of over $5 billion. Our team is fully focused on preparing for a successful commercial launch of UGN-102, if approved, in 2025."

Q3 2024 and Recent Business Highlights:

UGN-102 (mitomycin) for intravesical solution:

In October 2024, the U.S. Food and Drug Administration (FDA) accepted UroGen’s New Drug Application (NDA) for investigational drug UGN-102 (mitomycin) for intravesical solution as a treatment for low-grade intermediate risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The FDA granted a Prescription Drug User Fee Act (PDUFA) target action date of June 13, 2025.
The NDA for UGN-102 is supported by a comprehensive development program which demonstrated a clinically meaningful complete response rate and a strong duration of response across three late phase clinical trials and an acceptable safety profile. The Phase 3 ENVISION trial successfully met its primary endpoint by demonstrating that patients treated with UGN-102 had a 79.6% (95% CI, 73.9%, 84.5%) complete response (CR) rate at three months following the first instillation of UGN-102. More recently, durability data from ENVISION showed that UGN-102 demonstrated an 82.3% (95% CI, 75.9%, 87.1%) 12-month duration of response (DOR) by Kaplan-Meier estimate in patients who had achieved a complete response at three months after the first instillation of UGN-102. This is the highest DOR ever reported in this patient population. The ENVISION trial demonstrated that UGN-102 has an acceptable safety profile that is consistent with the side effect profile observed in previous clinical trials.
JELMYTO (mitomycin) for pyelocalyceal solution in low-grade upper tract urothelial cancer (LG-UTUC):

Generated net product revenue of $25.2 million in the third quarter of 2024, compared to $20.9 million in the third quarter of 2023, primarily driven by strong underlying demand growth and also reflecting non-patient purchases.
Next-generation novel mitomycin-based formulation for urothelial cancers

In October 2024, the first patient was dosed in the Phase 3 UTOPIA clinical trial of investigational drug UGN-103 (mitomycin) for intravesical solution in patients with LG-IR-NMIBC. UGN-103 is a next generation product that combines UroGen’s RTGel technology with a novel mitomycin formulation licensed from medac GmbH. UGN-103 is planned to follow the potential FDA approval and launch of UGN-102 for LG-IR-NMIBC. UroGen plans to initiate a Phase 3 study early next year to explore the safety and efficacy of UGN-104, its next generation product for the treatment of LG-UTUC. To learn more about the UTOPIA trial, refer to clinicaltrials.gov/NCT06331299.
In September 2024, UroGen received a Notice of Allowance from the United States Patent and Trademark Office for a patent application covering, among other things, the use of UGN-103 in the treatment of LG-IR-NMIBC. The U.S. patent, once issued, will have an expiration date in December 2041.
Corporate

In October 2024, UroGen appointed Chris Degnan as Chief Financial Officer. Mr. Degnan brings broad expertise in financial strategy, investor relations, SEC reporting, accounting and compliance, having previously held CFO roles at Galera Therapeutics and Verrica Pharmaceuticals. He replaced Don Kim who left the Company to pursue other opportunities.
Third Quarter 2024 Financial Results

JELMYTO Revenue: JELMYTO net product revenues were $25.2 million and $20.9 million for the three months ended September 30, 2024, and 2023, respectively.

R&D Expense: Research and development expenses for the third quarter of 2024 were $11.4 million, including non-cash share-based compensation expense of $0.6 million as compared to $10.2 million, including non-cash share-based compensation expense of $0.4 million, for the same period in 2023.

SG&A Expense: Selling, general and administrative expenses for the third quarter of 2024 were $28.9 million, including non-cash share-based compensation expense of $2.9 million. This compares to $21.8 million, including non-cash share-based compensation expense of $1.8 million, for the same period in 2023.

Financing on Prepaid Forward Obligation: UroGen reported non-cash financing expense related to the prepaid forward obligation to RTW Investments of $5.9 million in the third quarter of 2024, compared to $5.5 million in the same period in 2023.

Interest Expense on Long-Term Debt: Interest expense related to the outstanding $125 million term loan facility with funds managed by Pharmakon Advisors was $2.7 million in the third quarter of 2024, compared to $3.8 million in the same period in 2023.

Net Loss: UroGen reported a net loss of $23.7 million or ($0.55) per basic and diluted share in the third quarter of 2024 compared with a net loss of $21.9 million or ($0.68) per basic and diluted share in the same period in 2023.

Cash & Cash Equivalents: As of September 30, 2024, cash, cash equivalents and marketable securities totaled $254.2 million.

For further details on the Company’s financials, including results for the 9-month period ended September 30, 2024, refer to Form 10-Q, filed with the SEC.

2024 Revenue, Operating Expense, and RTW Expense Guidance: With respect to the Company’s previously provided full-year 2024 JELMYTO revenue guidance, the Company expects full-year revenues to be below the low end of the guidance range. The Company does expect JELMYTO to achieve low double-digit year-over-year revenue growth for the full year 2024. With respect to the Company’s previously provided full-year 2024 operating expenses guidance, the Company expects to be toward the midpoint of the guidance range, including non-cash share-based compensation expense of $9 to $13 million, subject to market conditions. The anticipated full year 2024 non-cash financing expense related to the prepaid obligation to RTW Investments is unchanged and expected to be in the range of $21 to $26 million. The rate for the cash component of the RTW obligation will be 13% of global net product sales of JELMYTO in 2024.

Conference Call & Webcast Information: Members of UroGen’s management team will host a live conference call and webcast today at 10:00 AM Eastern Time to review UroGen’s financial results and provide a general business update.

The live webcast can be accessed by visiting the Investors section of the Company’s website at View Source Please connect 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.

On November 6, 2024 Precision Biologics, Inc. reported that affinity maturation and characterization of its novel anti-core 2 O-glycan monoclonal antibody PB-223, will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting on November 7-8, 2024, George R. Brown Convention Center, Houston, Texas (Press release, Precision Biologics, NOV 6, 2024, View Source [SID1234647862]), USA, Poster title: Affinity Maturation and Characterization of a Novel O-glycan Epitope Targeting Anti-Human Carcinoma Monoclonal Antibody (mAb) PB-223

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Presentation of the poster will be made in person on the following dates and locations:

November 7th, 2024: SITC (Free SITC Whitepaper) Immune Engineering Workshop, 3.10 p.m-5 p.m. CST, George R. Brown Convention Center, Level 3 – Grand Ballroom AB, Houston, Texas, USA
November 8th, 2024: Poster Session Immuno-Engineering, abstract number 1101, 12:15–1:45 p.m. CST and 5:30-7 p.m. CST, George R. Brown Convention Center, Level 1-Exhibit Halls A B, Houston, Texas, USA
BACKGROUND:

PB-223 is an innovative mAb developed through immune engineering from the chimeric IgG1 NEO-102 (Ensituximab). It targets a unique core 2 O-glycan (variant of MUC5AC),

Preclinical and clinical data showed that NEO-102 specifically binds to and kills colorectal and pancreatic cancer cells through ADCC. NEO-102 did not bind to healthy tissues. In a phase 2 study, NEO-102 showed promising results in heavily pretreated patients with advanced, refractory metastatic colorectal cancer.

In general, the efficacy of using a monoclonal antibody as a single agent in cancer immunotherapy can be impaired not only by the resistance of cancer cells in the tumor microenvironment (TME), but also by a low binding affinity to target antigens expressed on cancer cells.

One strategy to improve the therapeutic efficacy of monoclonal antibodies is to enhance their binding affinity to target antigens.
STUDY PRESENTED AT SITC (Free SITC Whitepaper) 2024:

The objective of this study was to enhance the binding affinity of NEO-102 to its target antigen. By engineering the VH and VL sequences of NEO-102 through Fast Screening for Expression Biophysical Properties and Affinity (FASEA), while maintaining the binding specificity to the target antigen, allowed us to develop a new clone with a lower KD and markedly improved characteristics. This new biologic asset developed by affinity maturation was given the name PB-223.
Binding kinetics of PB-223 and NEO-102 to the target antigen were compared by ELISA. Results show that PB-223 has a KD of 4.5-fold less than NEO-102, suggesting a higher affinity for the target antigen by PB-223 compared to NEO-102.
The binding affinity of PB-223 and NEO-102 to various human tumor cell lines was also evaluated by flow cytometry. Flow cytometry analysis showed that PB-223 not only has markedly enhanced comparative binding to colorectal and pancreatic cancer cell lines recognized by NEO-102, but that PB-223 is also able to bind to many additional tumor cell lines that were not recognized by NEO-102.
Further study by O-glycan array analysis showed that 1) PB-223 binds specifically to core-2 O-glycans, and that 2) core 2 O-glycans recognized by PB-223 are expressed on tumor cell lines positive for PB-223 binding in flow cytometry.
Immunohistochemistry (IHC) analysis performed on human tumor tissues shows that PB-223 does not bind to healthy tissues. IHC analysis also shows that PB-223, in addition to binding to both colorectal cancer and pancreatic cancer, it also binds to additional tumor tissues not reactive with NEO-102, including triple negative breast cancer, prostate cancer, kidney cancer, head and neck cancer, liver cancer, and bladder cancer.
In addition, this study demonstrated that PB-223 is internalized into human cancer cell lines expressing core 2 O-glycans.
Findings from this study suggest that PB-223 has a strong binding affinity for human cancers expressing core 2 O-glycans and that PB-223 may be a potential candidate for the development of antibody-drug conjugates (ADC) for treatment of various human carcinomas.

On November 6, 2024 Barinthus Biotherapeutics plc (NASDAQ: BRNS), a clinical-stage biopharmaceutical company developing novel immunotherapeutic candidates that guide T cells to control disease, reported an overview of business updates and announced financial results for the third quarter of 2024 (Press release, Barinthus Biotherapeutics, NOV 6, 2024, View Source [SID1234647802]).

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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

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"We continue our strong execution on our clinical trials, completing enrollment in the HBV003 trial of VTP-300 in chronic hepatitis B, and advancing VTP-1000 in celiac disease into the clinic with the first in human study of the novel SNAP-TI platform," said Dr. Leon Hooftman, Chief Medical Officer of Barinthus Bio. "We expect a data rich fourth quarter from the VTP-300 chronic hepatitis B program, with updated interim readouts from both the HBV003 and IM-PROVE II trials accepted as late-breaking abstracts at the American Association for the Study of Liver Diseases (AASLD) – The Liver Meeting 2024. These updates will provide more mature data than previously disclosed as participants progress and move towards a potential functional cure."

Third Quarter 2024 and Recent Corporate Developments

VTP-300 (Chronic hepatitis B)
In September 2024, enrollment was completed in the HBV003 trial of VTP-300 in 121 adult participants with chronic hepatitis B. The Phase 2b trial is designed to obtain critical dosing information for a potential functional cure regimen for chronic hepatitis B, with participants receiving VTP-300 and low-dose (LD) nivolumab.
Earlier this year, interim data from the HBV003 trial was presented at the European Association for the Study of the Liver (EASL) Congress and demonstrated that treatment with VTP-300 and LD nivolumab was generally well-tolerated and led to a sustained decline in Hepatitis B surface antigen (HBsAg) levels. Seventy-six percent of participants (n=16/21) assessed for nucleos(t)ide analogue (NUC) therapy discontinuation met the criteria. Sixty-seven percent of participants (n=14/21) assessed for NUC discontinuation had HBsAg <10 IU/mL at Week 24 or later. Nineteen percent of the eligible participants (n=4/21) reached undetectable levels of HBsAg, with 2 of these patients maintaining undetectable levels for over 16 weeks.

VTP-1000 (Celiac Disease)
In September 2024, we initiated the first-in-human Phase 1 AVALON trial of VTP-1000 in adults with celiac disease. The randomized, placebo-controlled clinical trial, which includes a controlled gluten challenge, will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000.

VTP-850 (Prostate Cancer)
In October 2024, we announced that the PCA001 trial of VTP-850 in men with rising prostate-specific antigen (PSA) after definitive local therapy for prostate cancer (i.e., biochemical recurrence) had completed patient enrollment of 22 participants. The Phase 1 trial is designed to evaluate safety and efficacy, as measured by PSA and T cell response. We expect to have data from the Phase 1 trial in the first half of 2025.

Financial Update
In October 2024, we were informed that an additional $15.0 million of revenue was due to the Company from Oxford University Innovation (OUI) in relation to the Company’s share of royalties received by OUI, as a result of prior commercial sales of Vaxzevria by AstraZeneca. We expect that this additional cash, when received, will enable us to fund our research and development plans further into the second quarter of 2026.

Upcoming Milestones
VTP-300 (Chronic hepatitis B)
In the fourth quarter of 2024, we expect to announce updated data from the VTP-300 program in ongoing clinical trials in chronic hepatitis B at AASLD – The Liver Meeting 2024 scheduled from November 15-19, 2024 in San Diego, CA:
•Updated interim data from HBV003, the Phase 2b trial evaluating additional dosing of VTP-300 and timing of PD-1 inhibition, accepted as a late-breaking oral presentation.
•Updated interim data from the Phase 2a IM-PROVE II clinical trial evaluating the combination of VTP-300 and Arbutus Biopharma’s imdusiran, accepted as a late-breaking poster.

VTP-1000 (Celiac Disease)
In the first half of 2025, we expect to announce data from the single ascending dose part of the Phase 1 AVALON trial of VTP-1000 in adults with celiac disease.

VTP-850 (Prostate Cancer)

In the first half of 2025, we expect to announce results of the Phase 1 PCA001 trial of VTP-850 in men with rising PSA after definitive local therapy for prostate cancer (i.e., biochemical recurrence).

Third Quarter 2024 Financial Highlights

•Cash position: As of September 30, 2024, cash, cash equivalents and restricted cash were $106.1 million, compared to $117.8 million as of June 30, 2024. The net cash used in operating activities was $18.2 million in the third quarter of 2024, primarily resulting from the development of our pipeline and ongoing clinical trials, offset by $6.2 million due to the effect of foreign exchange rates on cash balances. Based on our current operating plans, we expect our available resources to fund operating expenses and capital expenditure requirements into the second quarter of 2026.

•Revenue: Revenue consisted of $15.0 million in the third quarter of 2024 compared to nil in the second quarter of 2024. Revenue was comprised of the Company’s share of royalties received by OUI as a result of prior commercial sales of Vaxzevria by AstraZeneca.There is no expectation of additional payments or that we will be notified of such payments in a timely manner.
•Research and development expenses: Research and development expenses were $11.1 million in the third quarter of 2024 compared to $11.7 million in the second quarter of 2024, with the decrease mainly attributable to a reduction in personnel-related costs as a result of the pipeline prioritization earlier in the year. The quarter-on-quarter R&D expense per program is outlined in the following table.

Period ended Three months ended September 30, 2024
Three months ended June 30, 2024
Change
$000 $000 $000
Direct research and development expenses by program:
VTP-200 HPV $ 246 $ 383 $ (137)
VTP-300 HBV 2,748 3,034 (286)
VTP-500 MERS1
40 304 (264)
VTP-600 NSCLC/ESCC2
108 24 84
VTP-850 Prostate cancer 914 414 500
VTP-1000 Celiac
1,751 1,371 380
Other and earlier stage programs 707 908 (201)
Total direct research and development expenses $ 6,514 $ 6,438 $ 76
Indirect research and development expenses:
Personnel-related (including share-based compensation)3
3,871 4,763 (892)
Facility related 214 342 (128)
Other indirect costs 540 119 421
Total indirect research and development expenses 4,625 5,224 (599)
Total research and development expense $ 11,139 $ 11,662 $ (523)

1The development of VTP-500 is funded pursuant to an agreement with the Coalition for Epidemic Preparedness Innovations (CEPI).
2The VTP-600 NSCLC/Esophageal Squamous-Cell Carcinoma (ESCC) Phase 1/2a trial is sponsored by Cancer Research UK.
3This includes $0.6 million of personnel-related indirect expenses relating to time spent progressing the VTP-500 MERS program funded by CEPI.
•General and administrative expenses: General and administrative expenses were $13.4 million in the third quarter of 2024, compared to $7.2 million in the second quarter of 2024. The increase of $6.2 million relates primarily to a loss of $7.7 million on foreign exchange in the third quarter of 2024, compared to a loss of $0.1 million in the second quarter of 2024.
•Net loss: For the third quarter of 2024, we generated a net loss attributable to shareholders of $8.1 million, or $(0.21) per share on both basic and fully diluted bases, compared to a net loss attributable to shareholders of $16.9 million, or $(0.43) per share on both basic and fully diluted bases in the second quarter of 2024.