On November 7, 2024 Mural Oncology plc (Nasdaq: MURA), a clinical-stage immuno-oncology company developing novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers, reported three poster presentations at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place November 6-10, 2024 in Houston (Press release, Mural Oncology, NOV 7, 2024, View Source [SID1234647937]).

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Data presented from the ARTISTRY-3 clinical trial of Mural’s lead candidate, nemvaleukin alfa (nemvaleukin), showed tumor site-specific pharmacodynamic activity and immune activation in patients with ovarian cancer and mucosal melanoma. In addition, Mural presented preclinical data from its interleukin (IL)-12 and IL-18 programs that supported the company’s unique protein engineering capabilities to overcome shortcomings associated with cytokines.

"To date, nemvaleukin, as both a single agent and in combination with PD-1, has shown durable antitumor activities with manageable safety profile in an outpatient setting. In order to make nemvaleukin treatment administration more convenient for both patients and providers, we initiated the ARTISTRY-3 clinical trial to evaluate the effects of a less frequent IV dosing schedule," said Sarina Piha-Paul, MD, Associate Professor, Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and senior author of the ARTISTRY-3 poster. "The data from ARTISTRY-3 reveal that less frequent IV dosing of nemvaleukin demonstrated tumor-site immune activation dominated by cytolytic effector NK cells and CD8+ T cells and further support the mechanism of action of nemvaleukin."

The details for the presentations are as follows, and all posters are available at muraloncology.com/publications.

Tumor microenvironment pharmacodynamic effect of nemvaleukin less frequent intravenous dosing in multiple solid tumors: results from the phase 1/2 ARTISTRY-3 study (Friday, Nov. 8: Abstract #217)
Nemvaleukin is a novel, engineered fusion protein designed to leverage antitumor effects of the IL-2 pathway while mitigating the hallmark toxicities that have historically limited its use. ARTISTRY-3, a phase 1/2 study, evaluated less frequent intravenous (LFIV) dosing of nemvaleukin in advanced solid tumors.

Paired biopsies were available from 8 patients across the three different dosing schedules of nemvaleukin (Schedule 1: dosing on day 1; Schedule 2: dosing on days 1 and 8; Schedule 3: dosing on days 1 and 4).

Collectively, LFIV nemvaleukin demonstrated tumor-site-specific pharmacodynamic activity and immune activation. Nemvaleukin treatment increased cytolytic NK and CD8 T cell densities in the tumor microenvironment. Density ratios of CD8 and NK cells relative to immune-suppressive Tregs were also favorable for the nemvaleukin LFIV regimen. The results were seen in biopsies from both mucosal melanoma and ovarian cancer tumors, supporting the hypothesis that nemvaleukin has the potential to recruit cytolytic effectors to poorly immunogenic tumor sites.

Mural is currently running two late-stage, potentially registrational trials in platinum-resistant ovarian cancer (ARTISTRY-7) and mucosal melanoma (ARTISTRY-6, cohort 2), with data readouts expected in late Q1/early Q2 2025 and Q2 2025, respectively.

Preclinical efficacy and immune activity of half-life extended IL-18 fusion proteins resistant to IL-18BP suppression (Saturday, Nov. 9: Abstract #1340)
IL-18 is a potent immune-stimulating cytokine, but it is limited by IL-18 binding protein (IL-18BP), a secreted high-affinity decoy receptor that neutralizes IL-18, thus limiting its activity over time. Mural’s protein engineering aims to address the shortcomings of native IL-18 in two ways. First through the introduction of mutations designed to minimally impact the native structure while eliminating binding to IL-18BP. Secondly, by extending the half-life of IL-18BP via fusion to a protein scaffold to increase the cytokine’s exposure, allowing for sustained immune stimulation.

In preclinical models, a weekly dosing regimen in mice provided durable immune responses and tumor growth inhibition. These mouse ortholog variants demonstrated resistance to IL-18BP and increased half-life, with durable expansion of immune-stimulating NK and CD8 T cells.

These studies support pursuit of IND-enabling studies for first-in-human clinical trials. Mural plans to nominate a development candidate for its IL-18 program by the end of 2024 and intends to submit an Investigational New Drug (IND) Application to the FDA in Q4 2025.

Modulation of IL-12p70 exposure and activity following sequential administration of tumor targeted self-assembling split IL-12 subunits (Saturday, Nov. 9: Abstract #1300)
IL-12p70 is a potent stimulator of the immune system with profound anti-tumor activity but very poor tolerability. Mural is developing an innovative approach to mitigate that toxicity by creating inactive split IL-12 subunits (IL-12p35 and IL-12p40) and assembling functional IL-12p70 predominantly in the tumor and tumor microenvironment.

In murine models, increasing the interval time between subunit injections or reducing the dose level of the second subunit effectively modulated serum drug concentration while maintaining IL-12 levels in the tumor. Pharmacokinetics and pharmacodynamics were also assessed in non-human primates, where the inactive subunits were assembled and formed functional IL-12p70 in the periphery.

Together, these data suggest Mural’s novel approach may unlock the potential of IL-12p70 as a therapeutic by mitigating the toxicity associated with systemic administration.

Mural plans to nominate a development candidate for its IL-12 program by the end of 2024.

On November 7, 2024 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the third quarter that ended September 30, 2024 (Press release, Monte Rosa Therapeutics, NOV 7, 2024, View Source [SID1234647936]).

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"We continue to make significant progress towards pioneering the discovery and development of highly selective molecular glue degraders against paradigm-shifting targets. The recently announced global license agreement with Novartis to advance VAV1-directed MGDs for immune-related conditions marks a transformative milestone towards that goal," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "We believe this agreement will accelerate and broaden the scope of clinical development of MRT-6160 across a spectrum of immune-mediated conditions while retaining substantial value for Monte Rosa. Moreover, the resources provided by this agreement are expected to meaningfully extend our cash runway and enable us to advance our pipeline to potential value-creating milestones and to further leverage our industry-leading QuEEN discovery engine to design and develop novel MGDs for previously undruggable targets across a variety of disease areas, including immunology and inflammation (I&I), cardiovascular, and metabolic diseases. We look forward to sharing initial clinical data from the ongoing Phase 1 study of MRT-6160 by Q1 2025."

Dr. Warmuth continued, "We have made significant progress advancing our second I&I program, MRT-8102, toward an expected IND application in the first half of 2025. Turning towards our oncology pipeline, we look forward to sharing updated clinical results from the Phase 1 dose escalation portion of the MRT-2359 study by year-end, and we’re pleased with the progress of our cell cycle portfolio, including the CDK2 and cyclin E1 programs, with both advancing towards development candidate nominations."

RECENT HIGHLIGHTS

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors

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Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). In June 2024, the Company announced that it had obtained encouraging initial safety and pharmacodynamic data from the 0.5 mg dose using the 21 days on, 7 days off regimen. Monte Rosa continues to evaluate a higher 0.75 mg, 21 days on, 7 days off dose cohort.

MRT-6160, VAV1-directed MGD for immune-mediated conditions

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In October, the Company announced a global exclusive development and commercialization license agreement with Novartis to advance VAV1 MGDs including MRT-6160, currently in Phase 1 clinical development for various immune-related conditions. Under the terms of the agreement, Novartis will obtain exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs and will be responsible for all clinical development and commercialization, starting with Phase 2 clinical studies. Monte Rosa remains responsible for completion of the ongoing Phase 1 clinical study of MRT-6160. Novartis has agreed to pay Monte Rosa $150 million upfront. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies, as well as tiered royalties on ex-U.S. net sales. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S. The agreement is subject to customary closing conditions including regulatory clearance.
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In August, Monte Rosa announced that the first participants had been dosed in an MRT-6160 Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study.

MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome

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In September, Monte Rosa presented preclinical data at the Inflammasome Summit demonstrating that its development candidate MRT-8102, a first-in-class NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, is a potent, selective, and durable molecular glue degrader of NEK7. The data provide preclinical proof of concept that a NEK7 MGD leads to inhibition of the NLRP3 inflammasome and IL-1 release to reduce the effects of inflammation, supporting the potential to address central and peripheral inflammatory disorders.
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Monte Rosa expects to submit an IND application for MRT-8102 in H1 2025.

CDK2 and Cyclin E1-directed MGD programs

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In October, Monte Rosa presented preclinical data at the 36th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on the potential of its cyclin E1 (CCNE1)-directed MGDs for the treatment of CCNE1-amplified solid tumors. The data demonstrated that Monte Rosa’s MGD degrades cyclin E1 with a high level of selectivity, sparing other closely related proteins, including other cyclins, and cyclin-dependent kinases (CDKs). The data also showed that a cyclin E1-directed MGD led to downstream pathway inhibition and induced tumor growth suppression and regression preferentially in CCNE1-amplified and over-expressing tumor cell lines and xenograft models. Cyclin E1 MGDs may represent a potential novel therapeutic approach by directly and selectively targeting a frequently amplified non-enzymatic driver oncogene relevant in multiple solid tumors.
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Monte Rosa is progressing both its CDK2 and cyclin E1-directed MGD programs to development candidate nominations.

QuEEN (Quantitative and Engineered Elimination of Neosubstrates) discovery engine

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In October, Monte Rosa made a preprint available in BioRxiv entitled, "Mining the Cereblon Target Space Redefines Rules for Molecular Glue-induced Neosubstrate Recognition," which demonstrates a vast expansion of what had been considered druggable within the cereblon target space. Monte Rosa has identified more than 1,600 proteins predicted to be compatible with cereblon across diverse target classes that can potentially be targeted with molecular glue degraders.

ANTICIPATED MILESTONES

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Announce the recommended Phase 2 dose and data from the Phase 1 dose escalation portion of the MRT-2359 Phase 1/2 study including safety, biomarker data, and clinical activity before the end of 2024. The Company also expects to provide guidance on Phase 2 expansion cohorts before year-end.
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Report initial data from the Phase 1 SAD/MAD study of MRT-6160 in healthy volunteers by Q1 2025. The Phase 1 study of MRT-6160 is designed to provide early insights into safety, pharmacokinetics, VAV1 protein degradation, and key downstream pharmacodynamic markers including CD69, IL-2, IL-6, and IL-17.
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Submit an IND application for MRT-8102 in H1 2025.
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Nominate a CDK2 program development candidate before year-end 2024.

UPCOMING INVESTOR CONFERENCES

Monte Rosa management will participate in the following investor conferences:

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Guggenheim Securities Healthcare Innovation Conference (Boston, Mass.) – Markus Warmuth, M.D., Chief Executive Officer, to participate in a fireside chat, November 11, 2024, at 3:30 p.m. EST.
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Jefferies London Healthcare Conference (London, UK) – November 19, 2024.

A webcast of the fireside chat will be accessible via the "Events & Presentations" section of Monte Rosa’s website at ir.monterosatx.com, and an archived version will be made available for 30 days following the presentation.

THIRD QUARTER 2024 FINANCIAL RESULTS

Collaboration revenue: Collaboration revenue for the third quarter of 2024 was $9.2 million. Collaboration revenue represents revenue recorded under the Roche license and collaboration agreement. No collaboration revenue was recognized during the same period in 2023.

Research and Development (R&D) expenses: R&D expenses for the third quarter of 2024 were $27.6 million, compared to $28.3 million during the same period in 2023. R&D expenses were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, the advancement of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine. Non-cash stock-based compensation constituted $2.6 million of R&D expenses for Q3 2024, compared to $2.3 million in the same period in 2023.

General and Administrative (G&A) expenses: G&A expenses for the third quarter of 2024 were $8.1 million compared to $8.7 million during the same period in 2023. G&A expenses included non-cash stock-based compensation of $1.6 million for the third quarter of 2024, compared to $2.2 million for the same period in 2023.

Net loss: Net loss for the third quarter of 2024 was $23.9 million, compared to $30.3 million for the second quarter of 2024.

Cash position and financial guidance: Cash, cash equivalents, restricted cash, and marketable securities as of September 30, 2024, were $247.1 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $267.1 million as of June 30, 2024. The end of Q3 cash position does not include the recently announced $150 million upfront payment due from Novartis, subject to customary closing conditions including regulatory clearance.

Based on current cash, cash equivalents, restricted cash, marketable securities, and the anticipated $150 million upfront payment due from Novartis, the Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into 2028.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. MRT-6160 has shown promising activity in preclinical models of multiple immune-mediated conditions. Under the terms of an agreement announced in October 2024, Novartis will obtain exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs, subject to customary closing conditions including regulatory clearance.

About MRT-8102

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.

On November 7, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T‑cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors or hematologic malignancies, reported financial results and business highlights for the third quarter ended September 30, 2024 (Press release, Lyell Immunopharma, NOV 7, 2024, View Source [SID1234647935]).

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"With our acquisition of ImmPACT now complete, we plan to accelerate the development of IMPT-314, a dual-targeting CD19‌/‌CD20 CAR T-cell product candidate we believe has the potential to deliver increased complete response rates with longer duration of response over approved CD19 CAR T-cell therapies for patients with aggressive B‑cell non‑Hodgkin’s lymphoma," said Lynn Seely, M.D., Lyell’s President and CEO. "We look forward to presenting the initial data from the Phase 1 trial of IMPT-314 at ASH (Free ASH Whitepaper) next month and expect to initiate a pivotal clinical trial in 2025. In addition, site selection and initiation is progressing well for our Phase 1 trial of LYL119, our next-generation ROR1‑targeted CAR T‑cell product candidate designed with four technologies to generate T cells with even greater capacity to resist exhaustion. Our strong cash position enables us to advance our pipeline through important clinical milestones and fund operations into 2027."

Third Quarter Updates and Recent Business Highlights

Lyell is advancing two wholly-owned product candidates: IMPT-314 is in Phase 1-2 clinical development and LYL119 is entering Phase 1 clinical development. Lyell is also advancing next-generation CAR T-cell product candidates for solid tumors, which are in preclinical development.

IMPT-314 – A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed for improved response rates with enhanced durability for the treatment of large B-cell lymphoma (LBCL)

IMPT-314 is an autologous CAR T-cell product candidate enriched with naïve and central memory T cells during the manufacturing process. The Phase 1-2 clinical trial is a multi-center, open-label clinical trial designed to evaluate the tolerability and clinical benefit of IMPT-314 in patients with relapsed/refractory LBCL and determine a recommended Phase 2 dose. The trial is enrolling three cohorts of patients including CAR T-naïve patients in the third-line setting, CAR T-naïve patients in the second-line setting and CAR T-experienced patients. IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.
Initial data from Phase 1-2 trial will be presented at the ASH (Free ASH Whitepaper) 2024 Annual Meeting on December 9, 2024.
Expect to initiate a pivotal trial in 2025 in patients with relapsed/refractory large B-cell lymphoma in the third-line setting who have not yet been exposed to CAR T-cell therapy.
LYL119 – A next-generation ROR1-targeted CAR T-cell product candidate enhanced with four stackable and complementary anti-exhaustion technologies

LYL119 is an autologous ROR1-targeted CAR T-cell product candidate enhanced with four novel technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology designed to enable T-cells to resist exhaustion and to enhance their stem-like qualities.
The Phase 1 trial is designed as an open‑label dose‑escalation and ‑expansion trial in patients with ROR1‑positive solid tumors and will initially enroll patients with ROR1‑positive platinum‑resistant ovarian cancer or endometrial cancer. It is estimated that approximately 50% of patients with ovarian cancer and approximately 50% of patients with endometrial cancer have ROR1‑positive tumors.
Presenting a poster at the SITC (Free SITC Whitepaper) 2024 Annual Meeting titled "Multiomic profiling of LYL119: A Reprogrammed ROR1 CAR T Product Generates T cells with Reduced Exhaustion and Enhanced Memory Characteristics Associated with Increased AP-1 and Reduced NR4A Bindings." In a validated preclinical xenograft model of non-small cell lung cancer, LYL119 achieves complete tumor control and prolonged survival even at very low doses compared to LYL797, Lyell’s first generation ROR1-targeted CAR T‑cell product candidate. The study presents potential molecular mechanisms underlying the functional reduction of T-cell exhaustion and enhancement of memory‑related characteristics of LYL119 CAR T cells after antigen encounter in vitro and in vivo.
Initial clinical data are expected in the second half of 2025.
Third Quarter Financial Results

Lyell reported a net loss of $44.6 million for the third quarter ended September 30, 2024, compared to a net loss of $50.9 million for the same period in 2023. Non‑GAAP net loss, which excludes non-cash stock-based compensation, non‑cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, was $37.1 million for the third quarter ended September 30, 2024, compared to $43.0 million for the same period in 2023.

GAAP and Non-GAAP Operating Expenses

Research and development (R&D) expenses were $39.5 million for the third quarter ended September 30, 2024, compared to $43.8 million for the same period in 2023. The decrease in third quarter 2024 R&D expenses of $4.3 million was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the third quarter ended September 30, 2024, were $35.9 million, compared to $40.5 million for the same period in 2023. The decrease in third quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses.
General and administrative (G&A) expenses were $11.8 million for the third quarter ended September 30, 2024, compared to $15.5 million for the same period in 2023. The decrease in third quarter 2024 G&A expenses was primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the third quarter ended September 30, 2024, were $7.8 million, compared to $9.5 million for the same period in 2023. The decrease in third quarter 2024 non-GAAP G&A expenses was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce.
A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under "Non-GAAP Financial Measures."

Cash, cash equivalents and marketable securities

Cash, cash equivalents and marketable securities as of September 30, 2024, were $460.7 million, compared to $562.7 million as of December 31, 2023. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027.

On November 7, 2024 Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) reported financial results for the three and nine months ended September 30, 2024, and provided an operating forecast and business update (Press release, Ligand, NOV 7, 2024, View Source [SID1234647934]). Ligand management will host a conference call and webcast today at 8:30 a.m. Eastern Time to discuss this announcement and answer questions.

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"We just had one of the best quarters of performance in the history of Ligand. This success is due to the ongoing strength of our growing portfolio of commercial-stage programs, and we are pleased to announce an increase in guidance for the second time this year," said Todd Davis, CEO of Ligand. "This quarter, we had several key portfolio events, including the successful commercial launches of Ohtuvayre and CAPVAXIVE as well as the full FDA approval of FILSPARI. We believe each of these products, along with our recently acquired QARZIBA, will be key drivers of revenue growth for Ligand in the coming years."

Third Quarter 2024 Financial Results

Total revenues and other income for the third quarter of 2024 were $51.8 million, compared with $32.9 million for the same period in 2023, with the 58% increase primarily due to an increase in royalty revenue and milestone payments earned upon the commercial launch of Verona Pharma plc’s (Nasdaq: VRNA) Ohtuvayre. Royalties for the third quarter of 2024 were $31.7 million, compared with $23.9 million for the same period in 2023, with the 33% increase primarily attributable to royalties earned on Ligand’s recently acquired product, QARZIBA, and an increase in sales of Travere Therapeutics’ (Nasdaq: TVTX) FILSPARI. Captisol sales were $6.3 million for the third quarter of 2024, compared with $8.6 million for the same period in 2023, with the change due to timing of customer orders. Contract revenue and other income was $13.8 million for the third quarter of 2024, compared with $0.4 million for the same period in 2023, with the increase driven by the $13.5 million milestone payment earned upon the commercial launch of Ohtuvayre.

Cost of Captisol was $2.4 million for the third quarter of 2024, compared with $3.5 million for the same period in 2023, with the change due to timing of customer orders of Captisol sales. Amortization of intangibles was $8.3 million for the third quarter of 2024, compared with $8.2 million for the same period in 2023. Research and development expenses were $5.7 million for the third quarter of 2024, compared with $5.5 million for the same period in 2023. General and administrative expenses were $24.5 million for the third quarter of 2024, compared with $14.7 million for the same period in 2023, with the increase primarily attributable to higher stock-based compensation driven primarily by a one-time non-cash stock award modification charge tied to the departure of Ligand’s former COO and operating costs associated with incubating the Pelthos Therapeutics business.
GAAP net loss from continuing operations was $7.2 million, or $0.39 net loss per share for the third quarter of 2024, compared with $10.3 million, or $0.59 net loss per share, for the same period in 2023. GAAP net loss from continuing operations for the third quarter of 2024 included $15.3 million loss from non-cash fair value adjustments on the company’s Agenus Inc. (Nasdaq: AGEN) derivative assets. Core adjusted net income from continuing operations for the third quarter of 2024 was $35.3 million, or $1.84 per diluted share, compared to $18.0 million, or $1.02 per diluted share, for the same period in 2023. We did not sell any shares of Viking Therapeutics (Nasdaq: VKTX) common stock in the third quarter of 2024 or 2023. The increase in core adjusted net income was driven primarily by the 58% increase in revenue. The definition of core adjusted net income (loss) is adjusted net income plus the after-tax impact from the realized gain from the sale of Viking Therapeutics common stock. See the table below for a reconciliation of net loss from continuing operations to core adjusted net income from continuing operations.
As of September 30, 2024, Ligand had cash, cash equivalents and short-term investments of $219.6 million which includes $63.3 million in Viking Therapeutics common stock. Ligand issued 334,325 shares under the company’s At-the-Market (ATM) equity offering program at a weighted average share price of $104.70 for gross proceeds of $35 million during the third quarter of 2024. Ligand may continue to issue shares of our common stock having an aggregate offering price of up to $65 million from time to time under terms of the ATM program.
Year-to-Date Financial Results
Total revenues and other income for the nine months ended September 30, 2024 were $124.3 million, compared with $103.2 million for the same period in 2023. Royalties for the nine months ended September 30, 2024 were $74.0 million, compared with $62.5 million for the same period in 2023, with the increase primarily attributable to royalties earned on QARZIBA and an increase in sales of Travere Therapeutics’ FILSPARI. Captisol sales were $23.0 million for the nine months ended September 30, 2024, compared with $24.5 million for the same period in 2023, with the change due to the timing of customer orders. Contract revenue and other income was $27.4 million for the nine months ended September 30, 2024, compared with $16.3 million for the same period in 2023, with the increase driven by milestone payments of $19.2 million earned from Verona Pharma upon the approval and commercial launch of Ohtuvayre.

Cost of Captisol was $8.2 million for the nine months ended September 30, 2024, compared with $8.9 million for the same period in 2023, with the change due to the timing of customer orders. Amortization of intangibles was $24.7 million for the nine months ended September 30, 2024, compared with $25.3 million for the same period in 2023. Research and development expenses were $17.0 million for the nine months ended September 30, 2024, compared with $19.0 million for the same period in 2023, with the decrease primarily attributable to lower employee related expenses and lab supplies resulting from the Pelican spin-off in September 2023. The decrease was partially offset by additional costs associated with incubating the Pelthos business. For the nine months ended September 30, 2024, general and administrative expenses were $53.0 million, compared to $36.8 million for the same period in 2023. This increase was primarily driven by higher stock-based compensation expenses related to new hire stock awards for business development and investment team members. Additionally, a one-time, non-cash stock award modification expense related to the departure of Ligand’s former COO and costs associated with incubating the Pelthos business contributed to the increase.

GAAP net income from continuing operations was $27.1 million, or $1.46 per diluted share for the nine months ended September 30, 2024, compared with $35.6 million, or $2.00 per diluted share, for the same period in 2023. The decrease in GAAP net income from continuing operations from the prior year period is due primarily to the impairment of the financial royalty asset related to Takeda Pharmaceuticals’ (NYSE:TAK) soticlestat and the decrease in investments in Primrose Bio in connection with the equity funding received by Primrose Bio in June and July 2024. Adjusted net income from continuing operations for the nine months ended September 30, 2024 was $130.8 million, or $7.04 per diluted share, compared to $83.0 million, or $4.71 per diluted share, for the same period in 2023. Excluding the impact of gains from sales of Viking Therapeutics stock, core adjusted net income from continuing operations for the nine months ended September 30, 2024 was $83.0 million, or $4.46 per diluted share, compared with $53.0 million, or $3.01 per diluted share, for the same period in 2023. The increase in core adjusted net income is primarily driven by the increase in revenue. See the table below for a reconciliation of net income from continuing operations to core adjusted net income from continuing operations.

2024 Financial Guidance
Ligand is increasing its 2024 full year financial guidance previously outlined in July. The company now expects total revenue of $160 million to $165 million (previously $140 million to $157 million) and is raising core adjusted earnings per diluted share to $5.50 to $5.70 (previously $5.00 to $5.50).
Royalties are expected to be $105 million to $108 million (previously $100 million to $105 million), sales of Captisol of $27 million to $29 million (previously $25 million to $27 million) and contract revenue of $28 million (previously $15 million to $25 million). This guidance excludes the $60 million realized gain from short-term investments on the sale of Viking Therapeutics stock.Adjusted Financial Measures
Ligand reports adjusted net income and adjusted net income per diluted share in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The company’s financial measures under GAAP include share-based compensation expense, amortization of debt-related costs, amortization related to acquisitions and intangible assets, amortization of financial royalty assets, changes in contingent liabilities, mark-to-market adjustments for amounts relating to its equity investments in public companies, excess tax benefit from share-based compensation, Pelthos operating loss, impairment of financial royalty assets, loss from equity method investment in Primrose Bio, income tax effect of adjusted reconciling items and others that are listed in the itemized reconciliations between GAAP and adjusted financial measures included at the end of this press release. A reconciliation of forward-looking non-GAAP core adjusted earnings per diluted share to the most directly comparable GAAP measures is not available without unreasonable effort, as certain items cannot be reasonably predicted because of their high variability, complexity and low visibility. Specifically, non-cash adjustments that could be made for changes in contingent liabilities, changes in the market value of its investments in public companies, share-based compensation expense and the effects of any discrete income tax items, directly impact the calculations of our core adjusted earnings per diluted share, which we expect to have a significant impact on our future GAAP financial results.

Third Quarter 2024 and Corporate Highlights
Portfolio Updates
FILSPARI
On September 5, Travere Therapeutics announced it received full FDA approval for FILSPARI for the treatment of IgA Nephropathy (IgAN) in adults. The FDA decision expands patient access to the first and only non-immunosuppressive therapy approved for the treatment of this rare progressive kidney disease.
On October 17, Travere Therapeutics and CSL Vifor announced that Swissmedic granted temporary marketing authorization for FILSPARI for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g). The Swissmedic approval was supported by results from the pivotal Phase 3 PROTECT Study of FILSPARI in IgA nephropathy (IgAN) and follows full marketing approval by the U.S. Food and Drug Administration in September 2024 and conditional marketing authorization by the European Medicines Agency in April 2024.
On October 26, Travere Therapeutics presented new data further demonstrating the clinical benefit of FILSPARI in IgAN and reinforcing its potential in focal segmental glomerulosclerosis (FSGS) at the American Society of Nephrology Kidney Week 2024. Presentations included new data from the SPARTAN Study which showed that nearly 60% of patients with IgAN achieved complete remission when using FILSPARI as a first-line treatment. In addition, presentations took place on the SPARTACUS Study, PROTECT open-label extension, and real-world evidence highlighting the initial safety and efficacy data of FILSPARI in IgAN in combination treatment with a SGLT2 inhibitor. A late-breaking presentation demonstrated sparsentan delivered rapid and sustained proteinuria reduction and long-term kidney health benefits in a subset of patients with genetic, often treatment resistant, FSGS.
Ohtuvayre
On November 4, Verona Pharma provided an update on the commercial launch of Ohtuvayre in the U.S. reporting net sales of $5.6 million and October net sales that exceeded total third quarter sales. Additionally, through October Verona Pharma reported more than 2,200 unique prescribers and more than 5,000 prescriptions were filled across a broad COPD population.

In September, Verona’s Pharma development partner in Greater China, Nuance Pharma (private), completed enrollment in its pivotal Phase 3 clinical trial evaluating Ohtuvayre for the maintenance treatment of COPD in China. Results from the trial are expected in 2025.
Other Programs
On October 23, Merck (NYSE: MRK) announced that the U.S. Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) voted to update the adult age-based pneumococcal vaccination guidelines and has recommended CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) for pneumococcal vaccination in adults 50 years of age and older. Additionally, ACIP shared clinical decision-making has also recommended a supplemental dose of CAPVAXIVE for adults 65 years of age and older who have completed their vaccine series with both PCV13 (pneumococcal 13-valent conjugate vaccine) and PPSV23 (pneumococcal 23-valent polysaccharide vaccine).
On October 9, Viking Therapeutics announced positive data from the company’s Phase 1b clinical trial of VK0214, a novel small molecule agonist of the thyroid hormone receptor beta (TRβ), in patients with X-linked adrenoleukodystrophy. Results from this study showed VK0214 to be safe and well-tolerated following once-daily dosing over the 28-day study period. In addition, significant reductions were observed in plasma levels of very long-chain fatty acids (VLCFAs) and other lipids, as compared to placebo. Ligand is entitled to a 3.5-7.5% royalty on future net sales of VK0214, as well as clinical, regulatory, and commercial milestones.
On July 1, Palvella Therapeutics (private) initiated SELVA, a 24-week, pivotal Phase 3, single-arm, baseline-controlled clinical trial of QTORIN rapamycin for the treatment of microcystic lymphatic malformations (MLM). The study’s primary and key secondary endpoints are clinician-reported outcomes and the study will enroll 40 subjects at leading vascular anomaly centers across the U.S.

Conference Call and Webcast
Ligand management will host a conference call today beginning at 8:30 a.m. Eastern Time (5:30 a.m. Pacific Time) to discuss this announcement and answer questions. To participate via telephone, please dial (888) 596-4144 using the conference ID 8755336. Callers outside the U.S. may dial +1(646) 968-2525. To participate via live or replay webcast, a link is available at View Source

On November 7, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), an artificial intelligence ("AI") company developing targeted and transformative cancer therapies using its proprietary RADR AI and machine learning ("ML") platform with multiple clinical-stage drug programs, reported operational highlights and financial results for the third quarter 2024, ending September 30, 2024 (Press release, Lantern Pharma, NOV 7, 2024, View Source [SID1234647933]).

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"Lantern is achieving remarkable momentum, balancing meticulous execution with innovation. While progressing on the initial positive results from our Harmonic trial in both the US and Asia, we are also advancing our RADR AI platform to strategically guide our therapeutic pipeline. The emerging combination therapy opportunities we are identifying for both LP-184 and LP-284 underscore the strength of our AI-guided approach. Seeing our drug candidates advance in clinical trials, with the potential to meaningfully impact cancer patients’ lives, reinforces our mission. Additionally, as Starlight Therapeutics enters its next chapter of growth in CNS cancers, we look ahead to our plans for a Phase1b/2 clinical trial for STAR-001. We remain focused on the objective of developing therapies—at a fraction of the cost and time of traditional drug development by using our AI platform and data-driven methodologies. Our goal is ultimately to address critical and often unmet patient needs in oncology," said Panna Sharma, President and CEO of Lantern Pharma.

Highlights of AI-Powered Pipeline:

● LP-300: The Harmonic Phase 2 Clinical Trial – The Phase 2 Harmonic trial is aimed at making a significant advancement in addressing an urgent unmet need for never-smoker patients with non-small cell lung cancer (NSCLC). In the initial safety lead-in cohort of 7 patients, LP-300 demonstrated encouraging preliminary results when combined with standard-of-care chemotherapy (pemetrexed and carboplatin), achieving an 86% clinical benefit rate and a 43% objective response rate. Of particular note, 3 patients achieved partial responses with an average tumor size reduction of 51%, while 3 additional patients achieved stable disease with an average tumor reduction of 13%. Importantly, these preliminary results were observed regardless of prior tyrosine kinase inhibitor (TKI) treatments, patient demographics, or metastatic disease sites, suggesting broad potential applicability across the never-smoker NSCLC population.

The trial’s safety profile has been especially promising, with no dose-limiting toxicities observed and no discontinuations due to LP-300 treatment-related toxicity. The most common adverse events were manageable decreases in white blood cell count and thrombocytopenia.

The Harmonic trial has now progressed to its randomization and expansion phase, which is designed to enroll up to an additional 84 patients in a 2:1 ratio comparing LP-300 plus standard-of-care chemotherapy versus chemotherapy alone. With regulatory approval to expand into multiple Asian countries, the trial is positioned to accelerate enrollment in the targeted patient population of never-smokers with NSCLC, which we believe represents a potential global market estimated at over $4 billion annually. Leading our Harmonic trial efforts in Japan is Dr. Yasushi Goto, a renowned physician and researcher at the National Cancer Center Japan, where the incidence of never-smoker NSCLC is more than double that of the United States. The company has also initiated five trial sites in Taiwan, where over 40% of the new lung cancer diagnoses are among never-smokers, strategically positioning the Harmonic trial in regions with the highest prevalence of the target patient population. Lantern believes that this improves the potential for drug-candidate LP-300 to develop collaboration and co-development partnerships with global biopharma companies with a primary focus in serving the Asian markets. The study’s co-primary endpoints are progression-free survival (PFS) and overall survival (OS), with planned interim analysis after 31 patients have experienced disease progression which is expected by mid 2025.

● LP-184 – LP-184 continues to advance through its Phase 1a first-in-human basket trial (NCT05933265) across multiple solid tumor indications. Nine patient cohorts have been successfully dosed at escalating dose levels, and no dose-limiting toxicities observed to date. The trial is actively enrolling patients with relapsed/refractory advanced solid tumors, including pancreatic cancer, glioblastoma (GBM), triple-negative breast cancer, and other solid tumor types with DNA damage response deficiencies. Based on pharmacokinetic analyses, the upcoming cohorts are expected to reach dosage levels where therapeutic concentrations should be attainable, with enrollment projected to complete this year and initial safety and molecular correlation data expected by year-end 2024 or early 2025.

The LP-184 development program received a significant boost with the FDA granting Fast Track Designation in glioblastoma, recognizing both the serious nature of GBM and the significant unmet medical need in this indication which affects more than 13,000 U.S. adults annually. Through Lantern’s wholly-owned subsidiary Starlight Therapeutics, LP-184 (designated as STAR-001 for CNS indications) is being positioned for a Phase 1b/2a clinical trial in recurrent GBM that is targeted to begin in early 2025. Lantern has also made important progress towards developing a quantitative PCR-based molecular diagnostic test that could help identify patients most likely to respond to LP-184 treatment. Lantern is in the process of validating the PCR assay with patient samples from the initial seven cohorts from the LP-184 Phase 1a trial and we plan on using the molecular correlations to power future development and trial design.

Additional ongoing preclinical studies continue to demonstrate LP-184’s potential, particularly in combination therapy settings with some of the most widely used FDA approved drugs. One of these combinations using an FDA approved agent, spironolactone, is directed at the treatment of GBM and will be part of the planned Phase 1b study. Recent data presented at scientific conferences has highlighted promising synergy when LP-184 is combined with various FDA-approved treatments, including PARP inhibitors and immune checkpoint inhibitors. LP-184 has also shown promise in cancers with DNA damage response deficiencies beyond deficiencies in homologous recombination repair, demonstrating synthetic lethality in indications beyond those traditionally considered for PARP inhibitors. With an estimated aggregate annual market potential of approximately $12+ billion across its target indications ($4.5+ billion for CNS cancers and $7.5+ billion for solid tumors), we believe LP-184 represents a significant commercial opportunity while potentially addressing critical unmet patient needs across multiple cancer types.

● LP-284 – The fourth cohort of patients are being dosed, and no dose-limiting toxicities have been observed in the LP-284 Phase 1a clinical trial. We are in the process of opening additional hematology-focused sites later this year, with the potential to advance to Phase 1b or 2 by early to mid 2025. LP-284 has shown nanomolar potency across multiple published in vitro and in vivo studies, including mantle cell lymphoma (MCL), double hit lymphoma (DHL), and other advanced NHL cancer subtypes with DNA damage response deficiencies, notably those with compromised functioning of the ataxia-telangiectasia mutated (ATM) gene due to mutations or deletions. Nearly all MCL, DHL, and HGBL patients relapse from the current standard-of-care agents and there is an urgent and unmet need for novel improved therapeutic options for these patients. In the US and Europe, MCL, DHL, and HGBLs are diagnosed in 16,000-20,000 patients each year and these indications represent an estimated annual market potential of over $3+ billion.

Third Quarter 2024 Financial Highlights

● Balance Sheet: Cash, cash equivalents, and marketable securities were approximately $28.1 million as of September 30, 2024, compared to approximately $41.3 million as of December 31, 2023. The quarterly cash burn rate continues to reflect our capital-efficient, collaborator-centered business model.

● R&D Expenses: Research and development expenses were approximately $3.7 million for the quarter ended September 30, 2024, compared to approximately $2.2 million for the quarter ended September 30, 2023.

● G&A Expenses: General and administrative expenses were approximately $1.5 million for the quarter ended September 30, 2024, compared to approximately $1.3 million for the quarter ended September 30, 2023.

● Net Loss: Net loss was approximately $4.5 million (or $0.42 per share) for the quarter ended September 30, 2024, compared to a net loss of approximately $3.2 million (or $0.29 per share) for the quarter ended September 30, 2023.

● Total Share and Warrant Count: During the three months ended September 30, 2024, the Company issued 2,088 shares of common stock relating to the cashless exercise of warrants to purchase 7,664 shares, which warrants were expiring. Also during the three months ended September 30, 2024, the Company issued 3,832 shares of common stock for aggregate proceeds of $11,994 relating to the exercise of warrants that were expiring. As of the date of this press release, the Company has 10,784,725 shares of common stock outstanding, and outstanding warrants to purchase 70,000 shares of common stock.

Additional Operational Highlights:

● Lantern is building an efficient internal clinical operations team that it is leveraging across a range of clinical activities, from project management to site startup through data and quality management, and as a result is expected to rely less on external CRO providers with the aim of further managing ongoing clinical trial costs.

● Lantern published new research in PLOS ONE highlighting its data-driven approach to ADC design and development. The publication, titled ‘Expanding the repertoire of Antibody Drug Conjugate (ADC) targets with improved tumor selectivity and range of potent payloads through in-silico analysis,’ demonstrates a multi-step filtering approach to identify optimal ADC targets and payloads. Starting with over 20,000 protein-coding genes, they systematically narrowed candidates using membrane protein status, expression levels in critical tissues, and surface protein validation. The study uniquely analyzed how 416 different mutations across 22 tumor types affect target expression, revealing how specific mutations like KRAS in pancreatic cancer and EGFR in gliomas influence target levels. The analysis identified 82 promising ADC targets and 729 potential payloads, including novel candidates and repurposing opportunities for existing compounds with picomolar to nanomolar potency. We believe this comprehensive approach provides a framework for developing more precise and effective ADC therapeutics and assessing the utility and viability of an ADC design earlier in the development process.

● New data and scientific findings conducted in conjunction with Drs. Yong Du and Shiaw-Yih (Phoebus) Lin at MD Anderson were presented at The Immuno-Oncology Summit 2024. The findings showcased what Lantern believes to be the role of LP-184 to be combined with checkpoint inhibitors to provide greater response in TNBC due to synergy and to potentially transform TNBC tumors that are unresponsive (cold) to checkpoint inhibitors to responsive (hot). The poster was titled: LP-184, a Novel Acylfulvene, Sensitizes Immuno-Refractory Triple Negative Breast Cancers (TNBCs) To Anti-PD1 Therapy by Affecting the Tumor Microenvironment.

● Lantern will host its final Webinar Wednesday of 2024 on December 11, 2024, focusing on the company’s unique ability to predict blood-brain barrier penetration of drug compounds. The webinar will also discuss future development plans and potential commercial availability of this RADR platform module, which leverages extensive molecular feature analysis enriched with proprietary insights and data. According to the Therapeutic Data Commons, a coordinated initiative to access and evaluate artificial intelligence capability across therapeutic modalities and stages of discovery, Lantern’s BBB algorithms are 5 of the top 10 performing algorithms on the "Leaderboard".

Earnings Call and Webinar Details:

Lantern will host its 3rd quarter 2024 earnings call and webinar today, November 7th, 2024, at 4:30 p.m. ET. A link to register can be accessed at: (LTRN: 3rd Quarter Earnings Call & Zoom link)