On August 6, 2024 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported financial results for the second quarter ended June 30, 2024, and provided corporate updates (Press release, Sensei Biotherapeutics, AUG 6, 2024, View Source [SID1234645436]).

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"Collectively, the clinical data presented on SNS-101 over the past six months demonstrated early signs of clinical activity in a patient population generally resistant to immunotherapy, a well-tolerated safety profile, and the avoidance of a pharmacokinetic sink that hindered first-generation approaches to targeting VISTA," said John Celebi, President and Chief Executive Officer. "We believe these data validate that a pH-selective approach can overcome the previous hurdles associated with targeting VISTA, and we look forward to advancing patient enrollment in dose expansion cohorts to inform our Phase 2 trial design. With cash runway into the fourth quarter of 2025, we believe we are well positioned to substantially progress SNS-101 as we seek to create value for Sensei’s stockholders by developing innovative new treatment options for patients."

Clinical Highlights and Milestones

SNS-101

SNS-101 is a conditionally active antibody harnessing the acidic tumor microenvironment to selectively target the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation). VISTA is implicated in numerous cancer indications and its expression correlates with low survival rates.

Sensei is conducting a multi-center Phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in patients with advanced solid tumors.

In May 2024, Sensei presented promising clinical data from the dose escalation portion of its Phase 1/2 trial of SNS-101 at the 2024 American Society of Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. As of the April 30, 2024 data cutoff, SNS-101 demonstrated preliminary evidence of promising clinical activity in multiple tumor types, a potentially best-in-class pharmacokinetic (PK) profile and was well tolerated alone and in combination with cemiplimab, with no dose-limiting toxicities observed.
Patient enrollment is advancing in the dose expansion portion of the Phase 1/2 study. The Company is on track to report initial data from the dose expansion cohorts and hold an end-of-Phase 1 meeting with the FDA by the end of 2024.
In April 2024, Sensei published a peer-reviewed research paper in Nature Communications describing the mechanism of action of SNS-101 selectively targeting the active form of VISTA within the tumor microenvironment.
Corporate Updates

Sensei announces the appointment of Josiah Craver effective as of July 22, 2024, as Senior Vice President of Finance. Mr. Craver brings extensive experience in finance and accounting. Prior to joining Sensei in July 2024, he was the SVP of finance and corporate controller at KALA BIO and held senior finance positions at Solid Biosciences, including VP of finance and corporate controller after starting his career at PricewaterhouseCoopers in the health industries audit practice primarily serving life science and biotech companies of all sizes. Mr. Craver holds a M.S. in Accountancy and is a Certified Public Accountant.
Second Quarter 2024 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $52.3 million as of June 30, 2024. Sensei expects its current cash balance to fund operations into the fourth quarter of 2025.

Research and Development (R&D) Expenses: R&D expenses were $4.6 million for the quarter ended June 30, 2024, compared to $4.8 million for the quarter ended June 30, 2023. The decrease in R&D expenses was primarily attributable to lower outside research fees and lower costs related to preclinical research, primarily offset by higher expenses associated with clinical trials.

General and Administrative (G&A) Expenses: G&A expenses were $3.2 million for the quarter ended June 30, 2024, compared to $5.4 million for the quarter ended June 30, 2023. The decrease in G&A expense was primarily attributable to decreased cost for external professional services.

Net Loss: Net loss was $7.1 million for the quarter ended June 30, 2024, compared to $9.4million for the quarter ended June 30, 2023.

On August 6, 2024 Aligos Therapeutics, Inc. (Nasdaq: ALGS, "Aligos"), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in liver and viral diseases, reported recent business progress and financial results for the second quarter 2024 (Press release, Aligos Therapeutics, AUG 6, 2024, View Source [SID1234645405]).

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"This quarter we continued to execute on our key clinical programs," stated Lawrence Blatt, Ph.D., MBA, Chairman, President, and Chief Executive Officer of Aligos Therapeutics. "We completed enrollment ahead of schedule for the Phase 2a HERALD study of our THR-β agonist drug candidate, ALG-055009, and we expect topline data in early Q4 2024. In addition, we presented data from ALG-000184 at the EASL Congress 2024, including new data from the HBeAg-negative cohort, that demonstrated no viral breakthrough and unprecedented reductions in viral markers of CHB. We also received positive regulatory feedback from the FDA supporting subsequent studies of chronic suppressive therapy with sustained HBV DNA suppression as the primary approvable endpoint. We look forward to continuing to develop our drug candidates for patients in need of better outcomes."

Recent Business Progress

Aligos Portfolio of Drug Candidates

ALG-055009: Potential best-in-class small molecule THR-β agonist for MASH

The Phase 2a HERALD study completed enrollment in May 2024
Topline HERALD data are anticipated in early Q4 2024
ALG-000184: Potential first-/best-in-class small molecule CAM-E for CHB

Interim data from Parts 3 and 4 of Study ALG-000184-201 were presented at the European Association for the Study of the Liver (EASL) Congress 2024 and showed consistent, potent antiviral activity across multiple cohorts of untreated chronic hepatitis B (CHB) patients
Data from ≤ 72 weeks following an oral daily dose of 300 mg ALG-000184 monotherapy demonstrated sustained HBV DNA suppression (Reported for the first time were the antiviral and safety data in HBeAg-negative CHB subjects who received a daily oral dose of 300 mg ALG-000184 monotherapy for ≤60 weeks. In all 11 (100%) subjects, complete suppression of HBV DNA (Dosing continues in this ongoing Phase 1a/1b study, with subjects planning to dose for up to 96 weeks. Additional interim data readouts are planned to be presented this year at the American Association for the Study of Liver Diseases (AASLD) conference
Received positive feedback from the FDA regarding future studies with sustained HBV DNA suppression as the primary efficacy endpoint, leading to the potential registration of ALG-000184 for the treatment of hepatitis B infection
Phase 2 enabling activities, including drug supply manufacturing, are underway
ALG-097558: Potential best-in-class small molecule pan-coronavirus protease inhibitor

Topline data presented at the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Annual Meeting demonstrated single (up to 2000 mg) and multiple (up to 800 mg Q12 for 7 days) doses of ALG-097558 were well tolerated in healthy volunteers with a pharmacokinetic (PK) profile supporting twice daily, ritonavir-free dosing without a food effect
Phase 2 enabling activities, including nonclinical and clinical studies, are underway with financial support from the NIH
Financial Results for the Second Quarter 2024

Cash, cash equivalents and investments totaled $94.5 million as of June 30, 2024, compared with $135.7 million as of December 31, 2023. We continue to believe our cash balance provides sufficient cash to fund planned operations through the end of 2025.

Net income for the three months ended June 30, 2024 was $5.1 million or basic and diluted net income per common share of $0.03, compared to net losses of $18.8 million or basic and diluted net loss per common share of $(0.43) for the three months ended June 30, 2023. Net income for the three months ended June 30, 2024 was primarily due to a decrease in the fair value of the Company’s warrant liability, which resulted in non-cash income of $30.5 million, or $0.19 per share, associated with the warrants issued in October 2023 as part of the private investment in public equity (PIPE) offering.

Research and development (R&D) expenses for the three months ended June 30, 2024 were $21.1 million, compared with $16.8 million for the same period of 2023. The increase was primarily due to an increase in third party expenses for clinical trials. Total R&D stock-based compensation expense incurred for the three months ended June 30, 2024 was $1.2 million, compared with $1.6 million for the same period in 2023.

General and administrative (G&A) expenses for the three months ended June 30, 2024 were $6.4 million, compared with $9.2 million for the same period of 2023. The decrease in G&A expenses for this comparative period is primarily due to a decrease in third party expenses including legal expenses. Total G&A stock-based compensation expense incurred for the three months ended June 30, 2024 was $0.9 million, compared with $1.6 million for the same period of 2023.

Interest and other income, net, for the three months ended June 30, 2024 was income of $31.7 million compared with income of $1.1 million for the same period of 2023. The change in interest and other income, net, is primarily due to a decrease of $30.5 million in the fair value of the company’s warrant liability, which resulted in non-cash income.

On August 6, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported a business update, and announced financial results for the second quarter ended June 30, 2024 (Press release, Ideaya Biosciences, AUG 6, 2024, View Source [SID1234645421]).

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"We made significant progress advancing four potential first-in-class precision medicine oncology clinical programs this past quarter, and we are on-track to deliver our fifth potential first-in-class program to the clinic this year in Werner Helicase. Importantly, we presented preliminary clinical proof of concept data for IDE397 monotherapy in MTAP-deletion urothelial and lung cancer, demonstrating the ability to deliver confirmed RECIST responses with a favorable AE profile. The IDE397 combination therapy trials in MTAP-deletion solid tumors with our collaborators continue to progress, with the first patient dosed in the Phase 1 trial evaluating IDE397 with Gilead’s Trodelvy, and continued dose escalation in the AMG 193 clinical combination with Amgen. We look forward to hosting an investor R&D Day that will profile our rapidly advancing potential first-in-class precision medicine oncology pipeline, where we are targeting multiple additional development candidates by the end of this year," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences.

"We were excited to share the compelling interim clinical data from the investigator- and company-sponsored Phase 2 trials of darovasertib in neoadjuvant UM, and look forward to discussing the registrational path forward with the FDA and providing our company-sponsored Phase 2 trial update in over 30 patients during the second half of this year. In addition, the most recent positive interim results observed with IDE397 monotherapy, in addition to the ongoing combination trials, bring us closer to potentially addressing a high unmet need in MTAP-deletion NSCLC, urothelial cancer and other solid tumors, and we are targeting developing a registrational plan in 2025. Separately, we anticipate initiating both the Phase 2 IDE161 monotherapy expansion cohort and the IDE161 in combination with KEYTRUDA cohort in the second half of 2024," said Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

Summary of Q2 and Recent Key Developments

Research and Clinical Development

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Darovasertib in neoadjuvant uveal melanoma (UM)
o
Interim data from the investigator-sponsored Phase 2 trial were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 meeting by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney, and the lead principal investigator of the study.
o
The company-sponsored Phase 2 trial has enrolled over 50 patients in 20 sites globally as of July 31, 2024; a clinical update from eight patients was provided. An additional clinical data update in over 30 patients is planned in the second half of 2024.
o
IDEAYA has scheduled a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a potential registrational trial for darovasertib in the neoadjuvant UM setting in the third quarter of 2024.
•
IDE397 in MTAP-Deletion Solid Tumors
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Selected 30 mg as move-forward Phase 2 expansion dose in MTAP-deletion urothelial cancer and squamous non-small cell lung cancer (NSCLC). Reported positive interim data from 18 evaluable urothelial cancer and NSCLC patients.
o
Announced first-patient-in (FPI) for Phase 1 trial evaluating IDE397 in combination with Gilead’s Trodelvy in MTAP-deletion urothelial cancer.
o
The IDE397 / AMG 193 clinical combination dose escalation is ongoing. In the past quarter, IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC.
•
Entered into an option and license agreement for a potential first-in-class B7H3/PTK7 topo-I-payload bispecific antibody drug conjugate (B7H3/PTK7 Topo-Payload BsADC)
program with Biocytogen Pharmaceuticals (Beijing) Co., Ltd. (Biocytogen) in July 2024. A development candidate nomination is targeted for the second half of 2024.
•
IDEAYA plans to host an Investor R&D Day in Q4 2024.
Corporate Development

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Raised gross proceeds of approximately $302.4 million in July 2024 through public offering, generating net proceeds of approximately $283.8 million.
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Appointed Daniel A. Simon as Chief Business officer. Mr. Simon brings over 18 years of experience at leading life science and strategy consulting companies.

Clinical Programs and Upcoming Milestones

Darovasertib (IDE196) Program in Tumors with GNAQ or GNA11 Mutations

Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary and metastatic UM. Darovasertib is currently being evaluated in four ongoing clinical trials. The darovasertib and crizotinib combination in MUM has FDA Fast Track designation:

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IDE196-002(NCT05987332) is a Phase 2/3 potentially registration-enabling clinical trial of darovasertib + crizotinib in first-line human leukocyte antigens HLA-A2*02:01(-) MUM. Triple digit patient enrollment has been achieved as of July 31, 2024.
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IDE196-001 (NCT03947385) is a Phase 1/2 clinical trial evaluating darovasertib + crizotinib in GNAQ/11 melanomas, including in MUM and metastatic cutaneous melanoma.
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Phase 2 trials of darovasertib as neoadjuvant / adjuvant therapy in primary UM:
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IDE196-009 (NCT05907954) is a company-sponsored Phase 2 trial evaluating darovasertib as neoadjuvant treatment of UM prior to primary interventional treatment of enucleation or radiation therapy, and as adjuvant therapy following the primary treatment.
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Interim efficacy and safety results were reported in conjunction with the Phase 2 investigator-initiated trial (IST) interim data ASCO (Free ASCO Whitepaper) 2024 presentation.
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Data from eight patients (six enucleation and two plaque eligible) who have been on darovasertib treatment for 4 months or more as of the database lock of May 24, 2024 demonstrated a median tumor shrinkage (maximum height/base/volume change) of approximately 40%/25%/72% and the majority of the six enucleation patients had reported Eye Saved (i.e., converted to plaque brachytherapy or external beam radiotherapy (EBRT) eligible).
▪
Darovasertib had a manageable adverse events (AEs) profile with no drug-related serious adverse events (SAEs) observed; drug-related AEs were predominantly Grade 1 or Grade 2 and approximately 13% of patients reported at least one drug-related Grade 3 AE.
▪
The trial has enrolled over 50 patients in 20 sites globally, as of July 31, 2024.
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An amendment to the study protocol was submitted to the FDA in July 2024 to enable dosing of darovasertib as neoadjuvant and adjuvant therapy up to 12 months each. As part of this amendment the number of patients in the study was increased from 82 to 122 patients and the part 2 of the study will, once the amendment is effective, consist of adjuvant treatment with darovasertib in combination with crizotinib for patients with disease characteristics suggesting high or intermediate risk of metastasis.
▪
Additional clinical efficacy update from the company-sponsored Phase 2 of darovasertib neoadjuvant UM trial in over 30 patients is anticipated in the second half of 2024.
o
NADOM (NCT05187884) is a Phase 2 neoadjuvant / adjuvant trial of darovasertib in ocular melanoma. This is an IST led by Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney with additional participating sites in Melbourne, Australia.
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Interim efficacy and safety results were presented at the ASCO (Free ASCO Whitepaper) 2024 meeting. As of the database lock on May 14, 2024, 13 patients had completed neoadjuvant treatment, 11 patients received adjuvant darovasertib after primary treatment of their UM, with five patients completing the planned six months of therapy. At that time, 75% (nine out of 12 enucleation patients) had confirmed Eye Saved (i.e., converted to plaque brachytherapy or EBRT). After six months, approximately 67% (eight out of 12 enucleation patients) observed greater than 30% tumor shrinkage (maximum volume change) and median tumor shrinkage (maximum volume change) was approximately 47%.
▪
Darovasertib monotherapy neoadjuvant treatment had a manageable AE profile with no drug-related SAEs observed. Drug-related AEs were predominantly Grade 1 or Grade 2 and 20% of patients reported at least one drug-related Grade 3 AE.
o
IDEAYA has scheduled a Type C meeting with the FDA in the third quarter of 2024 to discuss a potential registrational trial for darovasertib in the neoadjuvant UM setting.

IDE397 Program in Tumors with MTAP Deletion

IDE397 is a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2 alpha (MAT2A) in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion. IDEAYA continues to focus on evaluating IDE397 in two trials in select monotherapy indications and in high conviction clinical combinations:

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IDE397-001 (NCT04794699) is a Phase 1/2 treatment study with monotherapy expansion in MTAP-deletion NSCLC and urothelial cancer. The estimated U.S. MTAP-deletion annual incidence in NSCLC and urothelial cancer is approximately 48,000 patients.
o
Selected 30 mg as the move-forward expansion dose for IDE397 monotherapy in MTAP-deletion urothelial cancer and squamous NSCLC based on adverse event profile and preliminary clinical efficacy observed.
o
Over 35 global clinical trial sites activated to enable rapid enrollment.
o
Reported positive interim data from 18 evaluable MTAP-deletion urothelial and NSCLC patients by RECIST 1.1:
▪
~39% Overall Response Rate (ORR) observed with one complete response and six partial responses. Two partial responses were awaiting confirmation at the time of the update (July 8, 2024), and one urothelial cancer patient that had a 100% tumor reduction in the target lesion at the last CT-scan assessment has now been confirmed. The second adenocarcinoma NSCLC patient is still awaiting confirmation as of July 31, 2024
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In patients with urothelial cancer: One complete response and two partial responses were observed.
•
In patients with lung cancer: three partial responses were seen in squamous NSCLC patients, and one partial response seen in adenocarcinoma NSCLC patient. There was one non-evaluable patient who discontinued due to rapid clinical progression of cancer fatigue and drug-unrelated adverse events in cycle 1 of treatment.
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~94% Disease Control Rate (DCR) seen with one complete response, six partial responses, and 10 stable disease.
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~78% of patients (14/18) experienced tumor shrinkage.
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Preliminary durability assessment showed 11 of the 18 patients are still on treatment, and five of seven RECIST 1.1 responses remain in response. Median duration of treatment, median duration of response, and median progression free survival not yet reached.
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~81% circulating tumor DNA (ctDNA) Molecular Response (MR) Rate observed in evaluable subjects with 13 of 16 patients with 50% or greater ctDNA reduction. There were several quality control failures of patient samples that led to unavailability for MR analysis.
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Overall favorable AE profile. Approximately 5.6% grade 3 or higher drug-related AEs and no drug-related SAEs reported at IDE397 30 mg once-a-day expansion dose. No drug-related AEs leading to discontinuations observed. We anticipate that the favorable AE profile and dosing convenience of a 30 mg once-a-day tablet has the potential to enable long-term dosing and combination development.
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30 mg once daily expansion dose achieves target drug coverage and plasma S-adenosyl-l-methionine (SAM) pharmacodynamic reduction associated with preclinical tumor regressions.
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Targeting development of IDE397 registrational plan in MTAP-deletion solid tumors in 2025.
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Phase 1/2 trial of IDE397 and AMG 193 in MTAP-Deletion NSCLC (Amgen-sponsored study, NCT05975073)
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Targeting development of joint publication strategy on IDE397 and AMG193 combination in 2024.
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At this time, the IDE397 / AMG 193 clinical combination dose escalation is ongoing. In the past quarter, IDEAYA, in consultation with Amgen, has now financially budgeted to support its obligations for target IDE397 / AMG 193 clinical combination expansion in NSCLC.
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First patient dosed in the Phase 1 trial of IDE397 and Trodelvy in MTAP-deletion urothelial cancer (IDEAYA-sponsored,NCT04794699) evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy. The MAT2A-Trop2 antibody-drug conjugate (ADC) combination targets two distinct, yet complementary nodes in the 26% of patients with MTAP-deleted urothelial cancer and has first-in-class potential to improve clinical outcomes for urothelial cancer patients.

IDE161 Program in Tumors with Homologous Recombination Deficiency

IDE161 is a potential first-in-class inhibitor of poly(ADP-ribose) glycohydrolase (PARG), a novel, mechanistically distinct target in the same clinically validated biological pathway as poly(ADP-ribose) polymerase (PARP). IDE161 received two FDA Fast Track designations in platinum-resistant advanced or metastatic ovarian cancer patients having tumors with BRCA1/2 mutations, and in pretreated advanced or metastatic HR+, Her2-, BRACA1/2 mutant breast cancer. IDE161 is currently being evaluated as a monotherapy in IDE161-001 (NCT05787587), a Phase 1 trial of IDE161 in solid tumors with homologous recombination deficiency (HRD). Selection of an initial Phase 1/2 monotherapy expansion dose in HRD solid tumors remains on track for the second half of 2024. IDEAYA is currently validating IDE161 combination opportunities preclinically and targeting identification of additional combination(s) in 2024.

Additionally, IDEAYA is planning to evaluate IDE161 in combination with KEYTRUDA in patients with microsatellite instability (MSI)-high and microsatellite stable (MSS) endometrial cancer. Clinical first-patient-in for the IDE161 and KEYTRUDA combination is targeted in the second half of 2024.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

GSK-Partnered Programs

GSK101 (IDE705) Program in Tumors with HRD

GSK101 (IDE705) is a potential first-in-class small molecule inhibitor of Pol Theta Helicase being developed as a combination treatment with niraparib for advanced solid tumors with HRD. The

dose escalation portion of the GSK-sponsored Phase 1/2 clinical trial to evaluate GSK101 in combination with niraparib, the GSK small molecule inhibitor of PARP, for patients having solid tumors with BRCA or other HR mutations, or with HRD is currently ongoing.

Upon initiation of the Phase 1 dose expansion, IDEAYA will be eligible to receive a $10.0 million milestone payment, with the collaboration having a potential further aggregate later-stage development and regulatory milestones of up to $465.0 million. GSK is responsible for all research and development costs for the program. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, and tiered royalties on global net sales of GSK101 – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

Werner Helicase Inhibitor in Tumors with High MSI

IDEAYA and GSK remain on track for an IND filing in the second half of 2024 for the selected Werner Helicase inhibitor announced in December 2023. The IND-enabling Good Laboratory Practice (GLP) toxicology studies have been completed for the Werner Helicase inhibitor development candidate. IDEAYA has the potential to earn up to an additional $17.0 million in aggregate milestones through early Phase 1, including $7.0 million upon IND clearance, and is entitled to receive up to $465.0 million in further later-stage development and regulatory milestones. GSK is responsible for 80% of global research and development costs and IDEAYA is responsible for 20% of such costs. Upon commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones, 50% of U.S. net profits and tiered royalties on global non-U.S. net sales of the Werner Helicase inhibitor development candidate (DC) – ranging from high single-digit to sub-teen double-digit percentages, subject to certain customary reductions.

B7H3/PTK7 Topo-Payload BsADC Program

IDEAYA entered into an option and license agreement for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program with Biocytogen in July 2024. The agreement grants IDEAYA an option for an exclusive worldwide license from Biocytogen for a potential first-in-class B7H3/PTK7 Topo-Payload BsADC program. B7H3/PTK7 has been found to be co-expressed in multiple solid tumor types, including double-digit percent prevalence in lung, colorectal, and head and neck cancers, among others. Based on preclinical data, the potential first-in-class B7H3/PTK7 Topo-Payload BsADC program has the potential to be developed as a monotherapy agent and used in combination with multiple programs in IDEAYA’s pipeline targeting DDR-based therapies, including PARG inhibitor IDE161. A development candidate nomination for the B7H3/PTK7 Topo-Payload BsADC program is targeted for the second half of 2024.

Under the terms of the agreement, Biocytogen will receive an upfront fee and, upon an option exercise by IDEAYA, be entitled to receive an option exercise fee, development and regulatory milestones and commercial milestone payments, as well as single-digit royalties on net sales. Total potential upfront, option exercise and milestone payments equal an aggregate of $406.5 million, including development and regulatory milestones of $100.0 million.

Next-Generation Precision Medicine Pipeline Programs

Early preclinical research programs focused on pharmacological inhibition of several new targets for patients with solid tumors characterized by defined biomarkers based on genetic mutations and/or molecular signatures are ongoing. These programs have the potential for discovery and development of first-in-class or best-in-class therapeutics with multiple wholly owned DC nominations targeted in the second half of 2024, including in MTAP-deletion solid tumors indications to enable a potential wholly-owned clinical combination with IDE397 and the lysine acetyltransferase 6 (KAT6) pathway.

Financial Results

As of June 30, 2024, IDEAYA had cash, cash equivalents and marketable securities totaling $952.7 million. This compared to cash, cash equivalents and marketable securities of $941.4 million as of March 31, 2024. The increase was primarily attributable to net proceeds of $36.5 million from the sale of common stock shares through IDEAYA’s at-the-market offering program during the period from April 1, 2024 to June 30, 2024, partially offset by net cash used in operations.

Subsequent to the reporting period for the quarter ended June 30, 2024, IDEAYA announced the closing in July 2024 of an underwritten public offering of common stock and pre-funded warrants to purchase common stock, generating net proceeds of approximately $283.8 million, after deducting the underwriting discounts and commissions and estimated offering expenses payable by IDEAYA.

There was no collaboration revenue recognized for the three months ended June 30, 2024 similar to the three months ended March 31, 2024. We completed all performance obligations related to the upfront payment under the GSK collaboration agreement as of December 31, 2023. Future collaboration revenue recognized under the GSK collaboration agreement will be related to future milestone payments as they are earned.

Research and development (R&D) expenses for the three months ended June 30, 2024 totaled $54.5 million compared to $42.8 million for the three months ended March 31, 2024. The increase was primarily due to higher stock-based compensation expenses, clinical trial expenses, professional and outside services and consulting expenses.

General and administrative (G&A) expenses for the three months ended June 30, 2024 totaled $10.4 million compared to $8.2 million for the three months ended March 31, 2024. The increase was primarily due to higher stock-based compensation expenses, audit fees and consulting expenses.

The net loss for the three months ended June 30, 2024 was $52.8 million compared to the net loss of $39.6 million for the three months ended March 31, 2024. Total stock compensation expense for the three months ended June 30, 2024 was $9.7 million compared to $6.3 million for the three months ended March 31, 2024.

On August 6, 2024 Veracyte, Inc. (Nasdaq: VCYT) reported financial results for the second quarter ended June 30, 2024 (Press release, Veracyte, AUG 6, 2024, View Source [SID1234645437]).

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"Our exceptional second quarter results are a testament to the strength and robustness of Decipher and Afirma," said Marc Stapley, Veracyte’s chief executive officer. "With both tests clearly gaining share in their respective markets and plenty of headroom for durable future expansion, our confidence in their long-term prospects continues to grow. Meanwhile, our positive cash generation and class-leading profitability profile are fueling a portfolio of tests that are poised to drive meaningful advances in precision medicine."

Key Business Highlights
•Increased second quarter total revenue by 27%, to $114.4 million, compared to the second quarter of 2023.
•Grew total test volume to 39,023, an increase of 23% compared to the second quarter of 2023.
•Increased second quarter net income to $5.7 million and delivered adjusted EBITDA of $24.0 million, or 21% of revenue.
•Achieved record Decipher Prostate test volume of close to 19,900 tests, driven by recently updated NCCN* prostate cancer guidelines, in which the Decipher Prostate test received the highest-level rating among gene expression tests.
•Delivered record Afirma test volume of approximately 15,700 and received Medicare coverage for Afirma testing of patients with thyroid nodules classified as "Bethesda V," giving more patients annually access to the test.
•Reinforced Veracyte’s commitment to evidence expansion with three published Decipher Prostate test studies, including a real-world, population-based analysis of Decipher data linked to the National Cancer Institute’s SEER database demonstrating the test’s clinical utility and underscoring the power of the Veracyte Diagnostics Platform.
•Generated $26.7 million of cash during the second quarter to end the quarter with $235.9 million of cash and cash equivalents.

* National Comprehensive Cancer Network. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

A reconciliation of GAAP to non-GAAP financial measures has been provided in the tables included in this press release. An explanation of these measures is also included below under the heading "Note Regarding Use of Non-GAAP Financial Measures."

Second Quarter 2024 Financial Results

Total revenue for the second quarter of 2024 was $114.4 million, an increase of 27% compared to $90.3 million reported in the second quarter of 2023. Testing revenue was $107.0 million, an increase of 31% compared to $81.7

million in the second quarter of 2023, driven by the strong performance of our Decipher Prostate and Afirma tests. Product revenue was $3.9 million, a decrease of 3% compared to $4.0 million in the second quarter of 2023. Biopharmaceutical and other revenue was $3.6 million, a decrease of 22% compared to $4.6 million in the second quarter of 2023.

Total gross margin for the second quarter of 2024 was 68%, compared to 62% in the second quarter of 2023. Non-GAAP gross margin, which excludes the amortization of acquired intangible assets, stock-based compensation, other acquisition related expenses, and certain other adjustments was 71%, compared to 68% in the second quarter of 2023.

Operating expenses were $73.3 million for the second quarter of 2024. Non-GAAP operating expenses, which excludes amortization of acquired intangible assets, stock-based compensation, other acquisition related expenses, and other restructuring costs, grew 14% to $59.0 million compared to $51.7 million in the second quarter of 2023.

Net income for the second quarter of 2024 was $5.7 million, an improvement of 168% compared to the second quarter of 2023. Basic and diluted net earnings per common share was $0.07, an improvement of $0.19 compared to the second quarter of 2023. Non-GAAP diluted net earnings per common share was $0.30, an improvement of $0.18 compared to the second quarter of 2023. Net cash provided by operating activities in the first six months of 2024 was $20.6 million, an improvement of $6.1 million compared to the same period in 2023.

Adjusted EBITDA for the second quarter of 2024 was $24.0 million, an improvement of 118% compared to the second quarter of 2023, representing 21% of revenue compared to 12% of revenue respectively.

A reconciliation of GAAP to non-GAAP financial measures has been provided in the tables included in this press release. An explanation of these measures is also included below under the heading "Note Regarding Use of Non-GAAP Financial Measures."

2024 Financial Outlook

The company is raising full-year 2024 total revenue guidance to $432 million to $438 million, representing year-over-year growth of 20% to 21% and testing revenue growth of approximately 25%. This guidance range represents an increase compared to prior guidance of $402 million to $410 million. In addition, the company now expects cash, cash equivalents and short-term investments at the end of the year to be $260 million to $270 million compared to prior guidance of $236 million to $240 million.

Conference Call and Webcast Details

Veracyte will host a conference call and webcast today at 4:30 p.m. Eastern Time to discuss the company’s financial results and provide a general business update. The conference call will be webcast live from the company’s website and will be available via the following link: View Source The webcast should be accessed 10 minutes prior to the conference call start time. A replay of the webcast will be available for one year following the conclusion of the live broadcast and will be accessible on the company’s website at View Source

The conference call dial-in can be accessed by registering at the following link: https://register.vevent.com/register/BIbb7f6b70b4ce4820b6391059390d6139

On August 6, 2024 Amgen (NASDAQ: AMGN) reported financial results for the second quarter 2024 (Press release, Amgen, AUG 6, 2024, View Source [SID1234645406]).

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"With a strong, balanced portfolio of in-market products and a rapidly advancing pipeline of innovative medicines, we are confident in our ability to deliver attractive long-term growth," said Robert A. Bradway, chairman and chief executive officer.

Key results include:

For the second quarter, total revenues increased 20% to $8.4 billion in comparison to the second quarter of 2023.
Product sales grew 20%, driven by 26% volume growth, partially offset by 3% lower net selling price. Excluding sales from our Horizon Therapeutics (Horizon) acquisition, product sales grew 5%, driven by volume growth of 10%.
Twelve products delivered at least double-digit sales growth in the second quarter, including Prolia (denosumab), EVENITY (romosozumab-aqqg), Repatha (evolocumab), TEZSPIRE (tezepelumab-ekko), BLINCYTO (blinatumomab), and TAVNEOS (avacopan).
Our performance included $1.1 billion of sales from our rare disease products, driven by several first-in-class, early-in-lifecycle medicines, including TEPEZZA (teprotumumab-trbw), KRYSTEXXA (pegloticase), UPLIZNA (inebilizumab-cdon), and TAVNEOS (avacopan).
GAAP earnings per share (EPS) decreased 46% from $2.57 to $1.38, driven by higher operating expenses, including amortization expense from Horizon-acquired assets and incremental expenses from Horizon, partially offset by higher revenues.
GAAP operating income decreased from $2.7 billion to $1.9 billion, and GAAP operating margin decreased 16.5 percentage points to 23.7%.
Non-GAAP EPS decreased 1% from $5.00 to $4.97, driven by higher operating expenses, including incremental expenses from Horizon, and interest expense, partially offset by higher revenues.
Non-GAAP operating income increased from $3.5 billion to $3.9 billion, and non-GAAP operating margin decreased 4.4 percentage points to 48.2%.
The Company generated $2.2 billion of free cash flow in the second quarter of 2024 versus $3.8 billion in the second quarter of 2023, driven by the timing of tax payments. In 2023, federal tax payments, including our repatriation tax, were made in Q4, whereas in 2024 these payments were made in Q2.
References in this release to "non-GAAP" measures, measures presented "on a non-GAAP basis" and "free cash flow" (computed by subtracting capital expenditures from operating cash flow) refer to non-GAAP financial measures. Adjustments to the most directly comparable GAAP financial measures and other items are presented on the attached reconciliations. Refer to Non-GAAP Financial Measures below for further discussion.

Product Sales Performance

General Medicine

Repatha (evolocumab) sales increased 25% year-over-year to $532 million in the second quarter, driven by 46% volume growth, partially offset by 20% lower net selling price. Repatha remains the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader.

EVENITY (romosozumab-aqqg) sales increased 39% year-over-year to $391 million in the second quarter, primarily driven by volume growth.

Prolia (denosumab) sales increased 13% year-over-year to $1.2 billion in the second quarter, primarily driven by volume growth.
Oncology

BLINCYTO (blinatumomab) sales increased 28% year-over-year to $264 million in the second quarter, driven by broad prescribing across academic and community segments for patients with B-cell precursor acute lymphoblastic leukemia (B-ALL).

Vectibix (panitumumab) sales increased 9% year-over-year to $270 million in the second quarter, driven by higher net selling price and volume growth, partially offset by unfavorable foreign exchange impact.

KYPROLIS (carfilzomib) sales increased 9% year-over-year to $377 million in the second quarter, primarily driven by volume growth outside the U.S.

LUMAKRAS/LUMYKRAS (sotorasib) sales increased 10% year-over-year to $85 million in the second quarter, primarily driven by volume growth.

XGEVA (denosumab) sales increased 6% year-over-year to $562 million in the second quarter, driven by higher net selling price.

Nplate (romiplostim) sales increased 12% year-over-year to $346 million in the second quarter.

IMDELLTRA (tarlatamab-dlle) generated $12 million of sales in the second quarter. IMDELLTRA is the first and only FDA-approved bispecific T-cell engager (BiTE) therapy for the treatment of extensive-stage small cell lung cancer (ES-SCLC).

MVASI (bevacizumab-awwb) sales decreased 20% year-over-year to $157 million in the second quarter. Going forward, we expect continued sales erosion driven by competition.
Inflammation

TEZSPIRE (tezepelumab-ekko) sales increased 76% year-over-year to $234 million in the second quarter, primarily driven by volume growth. Healthcare providers recognize TEZSPIRE’s unique, differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe, uncontrolled asthma.

Otezla (apremilast) sales decreased 9% year-over-year to $544 million in the second quarter, primarily driven by 7% lower net selling price and 6% unfavorable changes to estimated sales deductions, partially offset by 2% volume growth.

Enbrel (etanercept) sales decreased 15% year-over-year to $909 million in the second quarter, primarily driven by lower net selling price. Going forward, we expect continued declining net selling price and relatively flat volumes.

AMJEVITA/AMGEVITA (adalimumab) sales decreased 11% year-over-year to $133 million in the second quarter. Ex-U.S. sales increased 8% year-over-year to $142 million, driven by volume growth. U.S. sales reflect lower net selling price and unfavorable changes to estimated sales deductions, partially offset by volume growth.
Rare Disease

Except for TAVNEOS, the products listed below were added through the acquisition of Horizon on Oct. 6, 2023.

TEPEZZA (teprotumumab-trbw) generated $479 million of sales in the second quarter. TEPEZZA is the first and only FDA-approved treatment for thyroid eye disease (TED).

KRYSTEXXA (pegloticase) generated $294 million of sales in the second quarter. KRYSTEXXA is the first and only FDA-approved treatment for chronic refractory gout.

UPLIZNA (inebilizumab-cdon) generated $92 million of sales in the second quarter. UPLIZNA is used to treat adults with neuromyelitis optica spectrum disorders.

TAVNEOS (avacopan) generated $71 million of sales in the second quarter. Sales increased 137% year-over-year, driven by volume growth. TAVNEOS is a first-in-class treatment for severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis).

Ultra rare products, which consist of RAVICTI (glycerol phenylbutyrate), PROCYSBI (cysteamine bitartrate), ACTIMMUNE (interferon gamma-1b), BUPHENYL (sodium phenylbutyrate) and QUINSAIR (levofloxacin), generated $187 million of sales in the second quarter.
Established Products

Our established products, which consist of EPOGEN (epoetin alfa), Aranesp (darbepoetin alfa), Parsabiv (etelcalcetide) and Neulasta (pegfilgrastim), generated $591 million of sales. Sales decreased 21% year-over-year for the second quarter, driven by unfavorable changes to estimated sales deductions and volume declines. In the aggregate, we expect the year-over-year volume declines for this portfolio of products to continue.
Product Sales Detail by Product and Geographic Region

$Millions, except percentages

Q2 ’24

Q2 ’23

YOYΔ

U.S

ROW

TOTAL

TOTAL

TOTAL

Repatha

$ 270

$ 262

$ 532

$ 424

25 %

EVENITY

281

110

391

281

39 %

Prolia

770

395

1,165

1,028

13 %

BLINCYTO

165

99

264

206

28 %

Vectibix

133

137

270

248

9 %

KYPROLIS

240

137

377

346

9 %

LUMAKRAS/LUMYKRAS

55

30

85

77

10 %

XGEVA

399

163

562

530

6 %

Nplate

214

132

346

310

12 %

IMDELLTRA

12

—

12

—

N/A

MVASI

100

57

157

197

(20 %)

TEZSPIRE

234

—

234

133

76 %

Otezla

432

112

544

600

(9 %)

Enbrel

902

7

909

1,068

(15 %)

AMJEVITA/AMGEVITA(1)

(9)

142

133

150

(11 %)

TEPEZZA(2)

478

1

479

—

N/A

KRYSTEXXA(2)

294

—

294

—

N/A

UPLIZNA(2)

77

15

92

—

N/A

TAVNEOS

61

10

71

30

*

Ultra rare products(2)

175

12

187

—

N/A

EPOGEN

32

—

32

61

(48 %)

Aranesp

91

257

348

365

(5 %)

Parsabiv

67

39

106

87

22 %

Neulasta

75

30

105

236

(56 %)

Other products(3)

292

54

346

306

13 %

Total product sales

$ 5,840

$ 2,201

$ 8,041

$ 6,683

20 %

*Change in excess of 100%

N/A = not applicable

(1) U.S AMJEVITA product sales for the three months ended June 30, 2024, were impacted by unfavorable
changes to estimated sales deductions

(2) Horizon-acquired products, and the Ultra rare products consist of RAVICTI, PROCYSBI, ACTIMMUNE,
BUPHENYL and QUINSAIR

(3) Consists of (i) KANJINTI, Aimovig, RIABNI, Corlanor, NEUPOGEN, AVSOLA, IMLYGIC, BEKEMV,
WEZLANA/WEZENLA and Sensipar/Mimpara, where Biosimilars total $183 million in Q2 ’24 and $130
million in Q2 ’23; and (ii) Horizon-acquired products including RAYOS and PENNSAID

Operating Expense, Operating Margin and Tax Rate Analysis

On a GAAP basis for the second quarter:

Total Operating Expenses increased 51% year-over-year. Cost of Sales as a percentage of product sales increased 13.1 percentage points driven by higher amortization expense from Horizon acquisition-related assets and, to a lesser extent, higher royalties and profit share, partially offset by the Puerto Rico excise tax. Research & Development (R&D) expenses increased 30% due to higher spend in later-stage clinical programs and research and early pipeline, including Horizon-acquired programs. Selling, General & Administrative (SG&A) expenses increased 38% primarily driven by the addition of Horizon and investments in our commercial brands. Other operating expenses consisted primarily of changes in the fair values of contingent consideration liabilities related to our Teneobio, Inc. acquisition from 2021.
Operating Margin as a percentage of product sales decreased 16.5 percentage points year-over-year to 23.7%.
Tax Rate decreased 8.6 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business.
On a non-GAAP basis for the second quarter:

Total Operating Expenses increased 30% year-over-year. Cost of Sales as a percentage of product sales increased 0.4 percentage points primarily driven by higher royalties and profit share, partially offset by Puerto Rico excise tax. R&D expenses increased 30% due to higher spend in later-stage clinical programs and research and early pipeline, including Horizon-acquired programs. SG&A expenses increased 36%, primarily driven by the addition of Horizon and investments in our commercial brands.
Operating Margin as a percentage of product sales decreased 4.4 percentage points year-over-year to 48.2%.
Tax Rate decreased 1.5 percentage points year-over-year primarily due to the change in earnings mix as a result of the inclusion of the Horizon business and net favorable items.
$Millions, except percentages

GAAP

Non-GAAP

Q2 ’24

Q2 ’23

YOYΔ

Q2 ’24

Q2 ’23

YOYΔ

Cost of Sales

$ 3,236

$ 1,813

78 %

$ 1,406

$ 1,142

23 %

% of product sales

40.2 %

27.1 %

13.1 pts

17.5 %

17.1 %

0.4 pts

Research & Development

$ 1,447

$ 1,113

30 %

$ 1,423

$ 1,092

30 %

% of product sales

18.0 %

16.7 %

1.3 pts

17.7 %

16.3 %

1.4 pts

Selling, General & Administrative

$ 1,785

$ 1,294

38 %

$ 1,686

$ 1,237

36 %

% of product sales

22.2 %

19.4 %

2.8 pts

21.0 %

18.5 %

2.5 pts

Other

$ 11

$ 82

(87 %)

$ —

$ —

N/A

Total Operating Expenses

$ 6,479

$ 4,302

51 %

$ 4,515

$ 3,471

30 %

Operating Margin

operating income as % of product sales

23.7 %

40.2 %

(16.5) pts

48.2 %

52.6 %

(4.4) pts

Tax Rate

6.0 %

14.6 %

(8.6) pts

14.9 %

16.4 %

(1.5) pts

pts: percentage points

N/A = not applicable

Cash Flow and Balance Sheet

The Company generated $2.2 billion of free cash flow in the second quarter of 2024 versus $3.8 billion in the second quarter of 2023 driven by the timing of tax payments. In 2023, federal tax payments, including our repatriation tax, were made in Q4, whereas in 2024 these payments were made in Q2.
The Company’s second quarter 2024 dividend of $2.25 per share was declared on March 6, 2024, and was paid on June 7, 2024, to all stockholders of record as of May 17, 2024, representing a 6% increase from this same period in 2023.
During the second quarter, the Company reduced debt outstanding by $1.4 billion. Year to date, the Company has reduced debt outstanding by $2.0 billion and remains on- track to deleverage, including greater than $10 billion of debt reduction by the end of 2025.
Cash and investments totaled $9.3 billion and debt outstanding totaled $62.6 billion as of June 30, 2024.
$Billions, except shares

Q2 ’24

Q2 ’23

YOYΔ

Operating Cash Flow

$ 2.5

$ 4.1

$ (1.7)

Capital Expenditures

$ 0.2

$ 0.3

$ 0.0

Free Cash Flow

$ 2.2

$ 3.8

$ (1.6)

Dividends Paid

$ 1.2

$ 1.1

$ 0.1

Share Repurchases

$ 0.0

$ —

$ 0.0

Average Diluted Shares (millions)

541

537

4

Note: Numbers may not add due to rounding

$Billions

6/30/24

12/31/23

YTD Δ

Cash and Investments

$ 9.3

$ 10.9

$ (1.6)

Debt Outstanding

$ 62.6

$ 64.6

$ (2.0)

Note: Numbers may not add due to rounding

2024 Guidance

For the full year 2024, the Company now expects:

Total revenues in the range of $32.8 billion to $33.8 billion.
On a GAAP basis, EPS in the range of $6.57 to $7.62, and a tax rate in the range of 6.0% to 7.5%.
On a non-GAAP basis, EPS in the range of $19.10 to $20.10, and a tax rate in the range of 15.0% to 16.0%.
Capital expenditures to be approximately $1.3 billion.
Share repurchases not to exceed $500 million.
Second Quarter Product and Pipeline Update

The Company provided the following updates on selected product and pipeline programs:

General Medicine
MariTide (maridebart cafraglutide, AMG 133)

MariTide, is a multispecific molecule that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon like peptide 1 (GLP-1) receptor.
A Phase 2 study of MariTide is ongoing in adults with overweight or obesity with or without type 2 diabetes mellitus. Topline data are anticipated in late 2024.
Planning for a broad Phase 3 program across multiple indications remains on track.
A Phase 2 trial investigating MariTide for the treatment of type 2 diabetes in patients with and without obesity is planned to initiate in late 2024.
Olpasiran (AMG 890)

Olpasiran is a potentially best-in-class small interfering ribonucleic acid (siRNA) molecule that reduces lipoprotein(a) (Lp(a)) synthesis in the liver.
The Ocean(a)-Outcomes trial, a Phase 3 cardiovascular outcomes study is ongoing in patients with atherosclerotic cardiovascular disease and elevated Lp(a).
Repatha

EVOLVE-MI, a Phase 4 study of Repatha administered within 10 days of an acute myocardial infarction to reduce the risk of cardiovascular (CV) events, has completed enrollment.
VESALIUS-CV, a Phase 3 CV outcomes study of Repatha, is ongoing in patients at high CV risk without prior myocardial infarction or stroke.
Oncology
IMDELLTRA

In May, the U.S. Food and Drug Administration (FDA) granted accelerated approval to IMDELLTRA, a first-in-class delta-like ligand 3 (DLL3) targeting BiTE (bispecific T-cell engager) molecule, for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. Additional regulatory submissions are underway or complete in countries outside of the U.S.
In May, the FDA granted orphan drug exclusivity for IMDELLTRA for treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.
IMDELLTRA was added to the SCLC National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology1 (NCCN guidelines) as a treatment option after first-line therapy. It is listed as a "Preferred Option" for patients with chemotherapy-free interval ≤ 6 months and as a "Other Recommended Treatment Option" for patients with chemotherapy-free interval > 6 months.
Advancing a comprehensive global clinical development program:
DeLLphi-304, a Phase 3 study comparing tarlatamab with standard of care chemotherapy in second-line ES-SCLC, has completed enrollment.
DeLLphi-305, a Phase 3 study comparing tarlatamab and durvalumab with durvalumab alone, is enrolling patients with first-line ES-SCLC.
DeLLphi-306, a Phase 3 study comparing tarlatamab with placebo following concurrent chemoradiation therapy, is enrolling patients with limited-stage SCLC.
DeLLphi-300, a Phase 1 study of tarlatamab, is ongoing in patients with relapsed /refractory SCLC.
DeLLphi-302, a Phase 1b study of tarlatamab in combination with AMG 404, is ongoing in patients with second-line or later SCLC. AMG 404 is an anti-programmed cell death protein 1 (PD1) monoclonal antibody.
DeLLphi-303, a Phase 1b study of tarlatamab in combination with standard of care, continues to enroll patients with first-line ES-SCLC.
DeLLpro-300, a Phase 1b study of tarlatamab, is ongoing in patients with de novo or treatment-emergent neuroendocrine prostate cancer.
In June, initial data were presented from:
The DeLLpro-300 study highlighting IMDELLTRA safety results with encouraging anti-tumor activity in DLL3-expressing de novo or treatment-emergent neuroendocrine prostate cancer.
A subgroup analysis of the Phase 2 DeLLphi-301 study demonstrating durable anticancer activity in relapsed / refractory SCLC regardless of the presence of treated, stable brain metastases at baseline.
Long-term follow-up data from the Phase 2 DeLLphi 301 study in patients with ES-SCLC who had failed two or more prior lines of treatment will be presented at the 2024 World Conference on Lung Cancer (WCLC) this fall.
BLINCYTO

In June, the FDA approved BLINCYTO for the treatment of adult and pediatric patients one month or older with CD19-positive Philadelphia chromosome (Ph)-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) in the consolidation phase, regardless of measurable residual disease (MRD) status. Additional regulatory submissions are underway or complete in countries outside of the U.S.
Data from the Phase 3 E1910 study were recently published in the New England Journal of Medicine. This study was in part the basis for the recent FDA approval and evaluated BLINCYTO in newly diagnosed B-ALL patients who were in remission and tested negative for MRD after an initial round of chemotherapy. At three years of follow-up, 85% of the patients who went on to receive additional standard consolidation chemotherapy plus BLINCYTO were alive, a significant improvement compared to 68% of patients who received chemotherapy only.
Golden Gate, a Phase 3 study of BLINCYTO alternating with low-intensity chemotherapy, continues to enroll older adult patients with newly diagnosed Ph-negative B-ALL.
A Phase 1/2 study of subcutaneous blinatumomab continues to enroll adult patients with relapsed or refractory Ph-negative B-ALL. The Company is planning to advance blinatumomab subcutaneous administration to a potentially registration-enabling Phase 2 portion of this study with initiation in H2 2025.
Xaluritamig (AMG 509)

Xaluritamig is a first-in-class bispecific T-cell engager targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1).
A Phase 1 monotherapy dose-expansion study of xaluritamig is ongoing in patients with metastatic castrate resistant prostate cancer (mCRPC) and continues to enroll patients to explore reduced monitoring after treatment administration. An outpatient treatment cohort has also been initiated to improve administration convenience.
A Phase 1 combination of xaluritamig with enzalutamide or abiraterone continues to enroll patients with mCRPC in dose escalation and dose expansion respectively.
Two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer are planned.
Updated results from the xaluritamig first-in-human trial, including longer follow-up and overall survival on the previously presented dose-escalation and initial results from dose optimization, will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in September.
AMG 193

AMG 193 is a first-in-class small molecule methylthioadenosine (MTA)-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor.
In August, the FDA granted an orphan drug designation to AMG 193 for the treatment of pancreatic cancer.
A Phase 1/1b/2 study of AMG 193 continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors in the dose-expansion portion of the study.
A Phase 1b study of AMG 193 alone or in combination with other therapies is enrolling patients with advanced MTAP-null thoracic tumors.
A Phase 1b study of AMG 193 in combination with other therapies was initiated in patients with advanced MTAP-null gastrointestinal, biliary tract, or pancreatic cancers.
A Phase 1/2 study of AMG 193 in combination with IDE397, an investigational methionine adenosyltransferase 2A (MAT2A) inhibitor, continues to enroll patients with advanced MTAP-null solid tumors.
Additional data from the Phase 1 dose escalation and initial dose expansion study of AMG 193 in patients with MTAP-null solid tumors will be presented at ESMO (Free ESMO Whitepaper) in September.
Nplate

A Phase 3 study of Nplate as supportive care in chemotherapy-induced thrombocytopenia in gastrointestinal malignancies is complete. Data analysis is ongoing with readout anticipated in H2 2024.
LUMAKRAS/LUMYKRAS

CodeBreaK 202, a Phase 3 study of LUMAKRAS plus chemotherapy vs. pembrolizumab plus chemotherapy, is enrolling patients with first-line KRAS G12C–mutated and programmed cell death protein ligand-1 (PD-L1) negative advanced non-small cell lung cancer (NSCLC).
Regulatory review by the European Medicines Agency (EMA) of the CodeBreaK 200 Phase 3 trial of adults with previously treated locally advanced or metastatic KRAS G12C–mutated NSCLC along with data from the Phase 2 dose-comparison substudy is ongoing.
A U.S. regulatory submission for the Phase 3 CodeBreaK 300 study of LUMAKRAS plus Vectibix vs. investigator’s choice of therapy in KRAS G12C–mutated metastatic colorectal cancer (CRC) was accepted under Priority Review with a Prescription Drug User Fee Act (PDUFA) date of October 17, 2024.
CodeBreaK 301, a Phase 3 study of LUMAKRAS in combination with Vectibix and FOLFIRI, is enrolling patients with first-line KRAS G12C–mutated CRC.
Bemarituzumab

Bemarituzumab is a first-in-class fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody.
FORTITUDE-101, a Phase 3 study of bemarituzumab plus chemotherapy, has completed enrollment in patients with first-line gastric cancer.
FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab in first-line gastric cancer, continues to enroll patients in the Phase 3 portion of the study.
FORTITUDE-103, a Phase 1b/2 study of bemarituzumab plus oral chemotherapy regimens with or without nivolumab continues to enroll patients in first-line gastric cancer.
FORTITUDE-301, a Phase 1b/2 basket study of bemarituzumab monotherapy, is ongoing in patients with solid tumors with FGFR2b overexpression.
Inflammation
TEZSPIRE

Data were presented from the COURSE Phase 2 study of TEZSPIRE in chronic obstructive pulmonary disease (COPD) demonstrating that TEZSPIRE numerically reduced the annualized rate of moderate or severe COPD exacerbations vs. placebo by 17% (90% CI: −6, 36; p=0.1042). Of note, greater reductions were observed in a subgroup of patients with baseline BEC ≥ 150 cells/μL (37% [95% CI: 7, 57]). The trend in reduction was highest in subjects with BEC ≥ 300 cells/µL. Planning for Phase 3 in COPD remains on track.
Based on the COURSE Phase 2 results, the FDA granted TEZSPIRE Breakthrough Therapy Designation as an add-on maintenance treatment of patients with moderate to very severe COPD characterized by an eosinophilic phenotype.
The DIRECTION Phase 3 study of TEZSPIRE in patients in China with a history of uncontrolled asthma met the primary endpoint, demonstrating a statistically significant reduction in annual asthma exacerbation rate (AAER) over 52 weeks compared to placebo.
A Phase 3 study of TEZSPIRE is ongoing in patients with chronic rhinosinusitis with nasal polyps. Data readout is anticipated in H2 2024.
A Phase 3 study of TEZSPIRE continues to enroll patients with eosinophilic esophagitis.
In severe asthma, the WAYFINDER Phase 3b study is fully enrolled. The PASSAGE Phase 4 real-world effectiveness study and the SUNRISE Phase 3 study continue to enroll patients.
Rocatinlimab (AMG 451/KHK4083)

Rocatinlimab is a first-in-class T-cell rebalancing monoclonal antibody targeting the OX40 receptor.
The eight study ROCKET Phase 3 program continues to enroll patients with moderate-to-severe atopic dermatitis. To date, over 3,100 patients have been enrolled in the ROCKET program, with five studies having completed enrollment.
The Phase 3 HORIZON study (part of the ROCKET program), evaluating rocatinlimab monotherapy vs. placebo in adults with moderate-to-severe atopic dermatitis, is ongoing. Data readout is anticipated in H2 2024.
A Phase 2 study of rocatinlimab is enrolling patients with moderate-to-severe asthma.
A Phase 3 study of rocatinlimab is enrolling patients with prurigo nodularis.
Otezla

In June data were presented:
Results from a real-world study comparing early vs. late Otezla treatment vs. topical therapy alone in mild-to-moderate psoriasis demonstrated that patients who initiated Otezla early were >50% more likely to achieve treatment goals of body surface area (BSA) ≤1% and BSA-75 at 6 months after treatment initiation compared with patients initiating a new topical treatment.
In the FOREMOST Phase 4 study, Otezla led to early improvement in clinical and patient reported outcomes in patients with oligoarticular psoriatic arthritis, which were sustained and further improved over 48 weeks with no new safety signals.
In the MOSAIC Phase 4 study in adults with active psoriatic arthritis, treatment with Otezla was associated with improvements in inflammation measured by MRI, clinical outcomes, and patient reported outcomes over 48 weeks of treatment.
Efavaleukin alfa (AMG 592)

Efavaleukin alfa is an interleukin 2 (IL 2) mutein Fc fusion protein.
A Phase 2b study of efavaleukin alfa continues to enroll patients with ulcerative colitis.
Ordesekimab (AMG 714/PRV-015)

Ordesekimab is a monoclonal antibody that binds interleukin-15.
A Phase 2b study of Ordesekimab is ongoing in nonresponsive celiac disease.
AMG 104 (AZD8630)

AMG 104 is an inhaled anti-thymic stromal lymphopoietin (TSLP) fragment antigen-binding (Fab).
Data were presented from the Phase 1 study of AMG 104 in healthy volunteers and patients with asthma. In this study AMG 104 demonstrated an acceptable safety profile and a significant reduction in fractional exhaled nitric oxide (FeNO) in patients with moderate-to-severe asthma and elevated FeNO.
The Company plans to initiate a Phase 2 study in patients with asthma in H2 2024.
Rare Disease
TAVNEOS

A Phase 3, open-label study of TAVNEOS in combination with Rituximab or a cyclophosphamide-containing regimen was initiated in children from 6 years to < 18 years of age with active ANCA-associated vasculitis (Granulomatosis with Polyangiitis (GPA) / Microscopic Polyangiitis (MPA)).
In June a post hoc subgroup analysis of the Phase 3 ADVOCATE trial was presented comparing TAVNEOS with steroid taper in patients with ANCA-associated vasculitis with ear, nose and throat (ENT) involvement at baseline. This analysis demonstrated that a higher proportion of patients receiving TAVNEOS had sustained remission at week 52 with the percentage of ENT manifestations also decreasing more rapidly with TAVNEOS treatment.
TEPEZZA

Regulatory review of the New Drug Application (NDA) for TEPEZZA in Japan and multiple additional geographies continues.
A Phase 3 study of TEPEZZA in Japan continues to enroll patients with chronic or low clinical activity score TED.
A Phase 3 study evaluating the subcutaneous route of administration of TEPEZZA is enrolling patients with TED.
UPLIZNA

In June, the Company announced positive topline results of a Phase 3 clinical trial evaluating the efficacy and safety of UPLIZNA for the treatment of Immunoglobulin G4-related disease (IgG4-RD). The trial met its primary endpoint, showing a statistically significant 87% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.13, p<0.0001) during the 52-week placebo-controlled period. All key secondary endpoints were also met and no new safety signals were identified. Full data from the trial will be presented at a future medical meeting. Regulatory filing activities are underway.
MINT, a Phase 3 study of UPLIZNA in patients with myasthenia gravis is ongoing. Data readout is anticipated in H2 2024.
Dazodalibep

Dazodalibep is a fusion protein that inhibits CD40L.
Two Phase 3 studies of Dazodalibep in Sjögren’s disease are enrolling patients. The first study is in patients with moderate-to-severe systemic disease activity, and the second study is in patients with moderate-to-severe symptomatic burden and low systemic disease activity.
In June, a manuscript based on data from the Phase 2 study of Dazodalibep in Sjögren’s disease was published in Nature Medicine.
Daxdilimab

Daxdilimab is a fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7).
A Phase 2 study of daxdilimab, is ongoing in patients with moderate-to-severe active primary discoid lupus erythematosus refractory to standard of care.
A Phase 2 study of daxdilimab is ongoing in patients with dermatomyositis and antisynthetase inflammatory myositis.
Fipaxalparant (formerly AMG 670/HZN 825)

Fipaxalparant is a lysophosphatidic acid receptor 1 (LPAR1) antagonist.
A Phase 2 study of fipaxalparant is ongoing in patients with idiopathic pulmonary fibrosis. Data readout is anticipated in H2 2024.
A Phase 2 study of fipaxalparant is enrolling patients with diffuse cutaneous systemic sclerosis.
Biosimilars

In May, the FDA approved BKEMV as the first interchangeable biosimilar to SOLIRIS (eculizumab).
The clinical comparative study portion of a randomized, double-blind pivotal study evaluating pharmacokinetic (PK) similarity of ABP 206 compared with OPDIVO (nivolumab) is enrolling patients with resected stage III or stage IV melanoma in the adjuvant setting.
A randomized, double-blind Phase 3 study to compare efficacy, pharmacokinetics, safety, and immunogenicity between ABP 234 and Keytruda (pembrolizumab) was initiated in patients with advanced or metastatic non-squamous non-small cell lung cancer.
TEZSPIRE is being developed in collaboration with AstraZeneca.
AMG 104 is being developed in collaboration with AstraZeneca
Rocatinlimab, formerly AMG 451/KHK4083, is being developed in collaboration with Kyowa Kirin.
Ordesekimab, formerly AMG 714 and also known as PRV-015, is being developed in collaboration with Provention Bio, a Sanofi Company. For the purposes of the collaboration, Provention Bio conducts a clinical trial and leads certain development and regulatory activities for the program.
Xaluritamig, formerly AMG 509, is being developed pursuant to a research collaboration with Xencor, Inc.
IDE397 is an investigational MAT2A inhibitor from IDEAYA Biosciences.
OPDIVO is a registered trademark of Bristol-Myers Squibb Company.
KEYTRUDA is a registered trademark of Merck & Co., Inc.
SOLIRIS is a registered trademark of ALEXION Pharmaceuticals, Inc.
1National Comprehensive Cancer Network (NCCN) makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.