On May 8, 2025 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 first quarter ended March 31, 2025 (Press release, Monte Rosa Therapeutics, MAY 8, 2025, View Source [SID1234652752]).

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

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

                  Schedule Your 30 min Free Demo!

"We’ve made significant progress across our entire portfolio in the development of our only-in-class and first-in-class molecular glue degrader therapeutics, targeting diseases poorly addressed by conventional pharmaceutical approaches," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "As highlighted in our recent pipeline update, our MRT-6160 Phase 1 study results support the broad potential application of this molecule as a novel treatment approach for immune-mediated diseases, and we are working diligently to advance the program into Phase 2 studies alongside our collaborators at Novartis. For our GSPT1 program, based on encouraging preliminary data from our ongoing Phase 1/2 study of MRT-2359 in MYC-driven solid tumors, we are focused on castration-resistant prostate cancer, an exciting opportunity in a population with widespread c-MYC expression. Study enrollment is ongoing, and we expect to report additional clinical data in H2 2025. Lastly, we continue to make excellent progress with our earlier stage programs. Our NEK7 program, targeting inflammatory diseases driven by IL-1β and the NLRP3 inflammasome, is on track, and we plan to file an IND submission for MRT-8102 in the first half of this year. Recent preclinical data for our CDK2-directed MGD highlight the substantially greater tumor regression achieved with our MGD combined with standard of care therapies compared to standard of care alone. We look forward to an IND submission for our CDK2 and/or CCNE1 cell cycle programs next year."

RECENT HIGHLIGHTS

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

•
In March 2025, Monte Rosa announced clinical results from its MRT-6160 Phase 1, single ascending dose / multiple ascending dose (SAD/MAD) study in healthy volunteers (clinicaltrials.gov identifier NCT06597799). The results support a clear path into anticipated Phase 2 studies and broad potential applications in multiple immune-mediated diseases. Further development of MRT-6160 toward Phase 2 studies is ongoing, in collaboration with Novartis.
•
Monte Rosa has a global exclusive development and commercialization license agreement with Novartis to advance VAV1 MGDs including MRT-6160. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies. 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., and is also eligible for tiered royalties on ex-U.S. net sales.

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

•
In March 2025, Monte Rosa provided updated clinical results in evaluating the safety, pharmacodynamics, and clinical activity of MRT-2359 in various tumor types. The Company has determined castration-resistant prostate cancer (CRPC) to be the primary MRT-2359 development focus. The Company continues to enroll and evaluate patients with CRPC, with the potential to expand enrollment to 20-30 patients if a positive efficacy signal continues to be observed, and expects to present additional results in H2 2025. Monte Rosa also continues to enroll and evaluate patients with HR+ breast cancer and expects to present additional results for this cohort in H2 2025.

NEK7-directed MGDs for inflammatory and CNS diseases driven by IL-1β and the NLRP3 inflammasome

•
Monte Rosa has successfully completed GLP tox studies for 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, supporting a considerable safety margin. The Company is on track to submit an IND application for MRT-8102 in H1 2025 and plans to initiate Phase 1 healthy volunteer and proof-of-concept studies in individuals with high levels of C-reactive protein (CRP) and in cardio-immunology indications. The Company continues to evaluate future Phase 2 proof-of-concept studies in gout, pseudogout (calcium pyrophosphate deposition disease), and osteoarthritis.

Cyclin E1 and CDK2-directed MGD programs for treatment of solid tumors

•
In April 2025, Monte Rosa presented preclinical data on the potential of its highly selective CDK2-directed molecular glue degrader, MRT-51443, to treat HR-positive/HER2-negative breast cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. MRT-51443 demonstrated superior anti-tumor activity in HR-positive/HER2-negative breast cancer models when combined with CDK4/6 inhibition and anti-estrogen therapy as compared to the standard-of-care combination of CDK4/6 inhibition and anti-estrogen therapy. Results also showed that MRT-51443 displayed superior selectivity compared to clinical-stage CDK2 inhibitors.

QuEEN (Quantitative and Engineered Elimination of Neosubstrates) discovery engine

•
Monte Rosa is advancing novel discovery programs for immunology and inflammation targets that the Company believes have the potential for highly differentiated, oral MGDs degrading undruggable targets in critical I&I pathways. These may include programs with the potential to improve upon the clinical profile of cell therapies, such as CAR-T, or biologics, such as FcRn inhibitors.

ANTICIPATED UPCOMING MILESTONES AND DEVELOPMENT PRIORITIES

•
Continue advancement of MRT-6160 toward Phase 2 initiation, in collaboration with Novartis.
•
Share additional MRT-2359 Phase 1/2 study data in CRPC patients resistant to androgen receptor (AR) therapy and in patients with HR+ breast cancer in H2 2025.
•
Submit an IND application for MRT-8102 in H1 2025.
•
Submit an IND application for the second-generation NEK7-directed MGD with enhanced CNS penetration in 2026.
•
Submit an IND application for a CDK2 and/or cyclin E1-directed MGD in 2026.

FIRST QUARTER 2025 FINANCIAL RESULTS

Collaboration revenue: Collaboration revenue for the first quarter of 2025 was $84.9 million and $1.1 million for the quarter ended March 31, 2024. Collaboration revenue represents amounts earned from our collaboration and license agreements with Roche and Novartis, primarily revenue recognized from the Novartis $150 million upfront payment in the fourth quarter of 2024 based on progress made on our performance obligations defined in the Novartis License Agreement.

Research and Development (R&D) Expenses: R&D expenses for the first quarter of 2025 were $32.2 million, compared to $27.0 million for the first quarter of 2024. These increases 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, including research performed in connection with our collaboration with Roche, the advancement of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine. Approximately $1.0 million included in R&D expenses are to be reimbursed pursuant to our license agreement with Novartis. Non-cash stock-based compensation constituted $3.1 million of R&D expenses for Q1 2025, compared to $2.7 million in the same period in 2024.

General and Administrative (G&A) Expenses: G&A expenses for the first quarter of 2025 were $8.7 million compared to $9.0 million for the first quarter of 2024. G&A expenses included non-cash stock-based compensation of $2.2 million for the first quarter of 2025, compared to $2.2 million in the same period in 2024.

Net Income (Loss): Net income for the first quarter of 2025 was $46.9 million, compared to a net loss of $32.0 million for the first quarter of 2024.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of March 31, 2025, were $331 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $377 million as of December 31, 2024. The decrease of $46 million was primarily due to the operational use of cash and one-time payments not recorded in operating expenses, including $12.2 million of value-added tax (VAT) collected from Novartis in the fourth quarter of 2024 in connection with the Novartis $150 million upfront payment and remitted to the Swiss Federal Tax Administration in the first quarter of 2025.

Based on current cash, cash equivalents, restricted cash, marketable securities, the Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into 2028.

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 is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to immune cells, including T and B cells. MRT-6160 has shown promising activity in preclinical models of multiple immune-mediated conditions. In a Phase 1, single ascending dose / multiple ascending dose (SAD/MAD) study in healthy subjects (clinicaltrials.gov identifier NCT06597799), MRT-6160 demonstrated sustained, dose-dependent VAV1 degradation in peripheral blood T and B cells after single and multiple dose administration. MRT-6160 also substantially inhibited secretion of inflammatory cytokines from whole blood derived T and B cells following ex vivo stimulation. Under the terms of an agreement announced in October 2024, Novartis has exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies. 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., and is also eligible for tiered royalties on ex-U.S. net sales.

About MRT-2359
MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) of GSPT1. 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. MRT-2359 is being investigated in an ongoing Phase 1/2 study (clinicaltrials.gov identifier NCT05546268) in solid tumors, including castration-resistant prostate cancer (CRPC). In CRPC patients resistant to AR therapy, a patient group characterized by widespread expression of c-MYC, MRT-2359 demonstrated encouraging early signals of clinical response.

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 cardiovascular disease, gout, osteoarthritis, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, and metabolic disorders. 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 and caspase-1 following ex vivo stimulation of whole blood. MRT-8102 has demonstrated a considerable safety margin (>200-fold exposure margin over projected human efficacious dose) in GLP toxicology studies.

On May 8, 2025 Manhattan BioSolutions, Inc. ("Manhattan Bio" or "MABS") reported that a collaborative project with Dr. Iwao Ojima’s laboratory at Stony Brook University has been awarded a REACH (Research Evaluation and Commercialization Hub) Feasibility Award from the Center for Biotechnology (CfB) at Stony Brook University (Press release, Manhattan BioSolutions, MAY 8, 2025, View Source [SID1234652751]). The award will advance their next-generation antibody-drug conjugate (ADC) platform incorporating proprietary Taxoid (TxD) payloads. This innovative technology leverages clinically validated taxane chemistry with novel modifications designed to enhance potency and overcome common resistance mechanisms in solid tumors.

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

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

                  Schedule Your 30 min Free Demo!

The awarded project is led by Principal Investigator Dr. Iwao Ojima, Distinguished Professor and Director of the Institute of Chemical Biology & Drug Discovery (ICB&DD) at Stony Brook University, and Co-Principal Investigator Dr. Boris Shor, CEO of Manhattan Bio. This work builds upon their existing partnership announced last year to develop innovative taxoid-based ADC payloads for solid tumors with high unmet medical need.

"This REACH award represents an important step in our ongoing collaboration with Professor Ojima’s laboratory," said Dr. Shor. "The CfB’s support will enable us to accelerate the development of this next-generation ADC platform incorporating structurally optimized derivatives of one of the most clinically established anticancer drug classes. These novel payloads demonstrate enhanced stability and significant potency against drug-resistant solid tumors, addressing key limitations of current ADC approaches."

The REACH program, administered by the CfB at Stony Brook University, is specifically designed to bridge the critical funding gap between academic discovery and commercial development. It provides targeted funding and strategic guidance to accelerate the translation of high-potential innovations in the biomedical field.

The TxD technology enhances Manhattan Bio’ ADC capabilities by adding a powerful payload class that complements the company’s existing ADC arsenal and is being validated with selected well-established solid tumor targets, creating a versatile foundation for future therapeutic development, including potential dual-warhead configurations.

On May 8, 2025 Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) reported financial results for the three months ended March 31, 2025, and provided an operating forecast and business update. Ligand management will host a conference call and webcast today at 8:30 a.m. Eastern Time to discuss this announcement and answer questions (Press release, Ligand, MAY 8, 2025, View Source [SID1234652750]).

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

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

                  Schedule Your 30 min Free Demo!

"Ligand delivered another strong quarter, reflecting the continued strength of our growing commercial royalty portfolio," said Todd Davis, CEO of Ligand. "We also took a significant strategic step to accelerate the commercial launch of ZELSUVMI through our recently announced transaction with Channel Therapeutics. This deal includes substantial financial backing from a group of strategic investors, and we believe it will create significant value for stockholders through both equity and royalty participation. In today’s challenging biopharmaceutical financing environment, our royalty aggregation model stands out as a resilient and proven strategy."

First Quarter 2025 Financial Results

Total revenues and other income for the first quarter of 2025 were $45.3 million, compared with $31.0 million for the same period in 2024, with the 46% increase primarily attributable to an increase in royalty revenue and Captisol sales. Royalties for the first quarter of 2025 were $27.5 million, compared with $19.1 million for the same period in 2024, with the 44% increase primarily attributable to royalties earned on Recordati’s Qarziba, and Travere Therapeutics’ Filspari. Captisol sales were $13.5 million for the first quarter of 2025, compared with $9.2 million for the same period in 2024, with the change due to the timing of customer orders. Contract revenue and other income was $4.4 million for the first quarter of 2025, compared with $2.7 million for the same period in 2024.

Cost of Captisol was $4.8 million for the first quarter of 2025, compared with $2.9 million for the same period in 2024, with the change due to an increase in Captisol sales. Amortization of intangibles was $8.3 million for the first quarter of 2025, compared with $8.2 million for the same period in 2024. Research and development expenses were $50.1 million for the first quarter of 2025, compared with $6.0 million for the same period in 2024, with the increase primarily attributable to a $44.3 million one-time charge in connection with our previously announced royalty financing agreement with Castle Creek Biosciences to fund the Phase 3 clinical study of D-Fi (FCX-007), which is accounted for as a research and development funding arrangement under ASC 730-20, Research and Development Arrangements. General and administrative expenses were $18.8 million for the first quarter of 2025, compared with $11.0 million for the same period in 2024, with the increase primarily attributable to employee related costs and operating costs associated with incubating the Pelthos business. Fair value adjustment to partner program derivatives was $(0.4) million for the first quarter of 2025 primarily due to mark to market adjustments to certain Agenus partnered programs.

GAAP net loss was $42.5 million, or $2.21 per share for the first quarter of 2025, compared with GAAP net income of $86.1 million, or $4.75 per diluted share, for the same period in 2024. Core adjusted net income for the first quarter of 2025 was $26.6 million, or $1.33 per diluted share, compared to $21.8 million, or $1.20 per diluted share, for the same period in 2024. Core adjusted net income excluded gains from the sale of Viking Therapeutics common stock in the first quarter of 2024. We did not sell any shares of Viking Therapeutics common stock in the first quarter of 2025. The increase in core adjusted net income was driven primarily by the 46% increase in revenue. Core adjusted net income represents a non-GAAP financial measure. See the table below for a reconciliation of net income (loss) to core adjusted net income.
As of March 31, 2025, Ligand had cash, cash equivalents and short-term investments of $208.9 million, which includes $24.2 million in Viking Therapeutics common stock.
2025 Financial Guidance
Ligand is reaffirming its 2025 full year financial guidance. The Company continues to expect 2025 royalty revenue ranging from $135 million to $140 million, revenue from sales of Captisol ranging from $35 million to $40 million and contract revenue ranging from $10 million to $20 million. These revenue components result in a total revenue forecast of $180 million to $200 million. Ligand notes that with total revenue of $180 million to $200 million, adjusted earnings per diluted share are anticipated to range from approximately $6.00 to $6.251.
First Quarter 2025 and Corporate Highlights

Pelthos Therapeutics Transaction

On April 17, Ligand announced the signing of a definitive merger agreement to combine Ligand’s wholly owned subsidiaries, Pelthos Therapeutics Inc. and LNHC, Inc. (collectively "Pelthos") with CHRO Merger Sub Inc., a wholly owned subsidiary of Channel Therapeutics. The merger will be supported by $50 million in capital raised from a group of strategic investors led by Murchinson ("Investor Group"). Upon completion of the transaction, the combined company will operate under the name Pelthos Therapeutics Inc. and trade on the NYSE American exchange under the ticker PTHS. The transaction is expected to close in the summer of 2025, subject to the fulfillment of customary closing conditions.
Under the terms of the merger agreement, Channel will acquire 100% of the issued and outstanding equity interests of Pelthos, and will change its name to Pelthos Therapeutics Inc. In connection with the transaction, Ligand has agreed to invest $18 million in the combined company and the Investor Group has agreed to invest $32 million for a total of $50 million.

The combined company will initially focus on accelerating the commercialization of Pelthos’ ZELSUVMI (berdazimer) topical gel, 10.3%, for the treatment of Molluscum contagiosum infections ("molluscum") in adults and pediatric patients one year of age and older. ZELSUVMI was approved by the U.S. Food and Drug Administration (FDA) in 2024 and is the first and only prescription therapy for molluscum infections approved for use at home by patients, parents, and caregivers.

New Royalty Investment
On February 25, Ligand announced that it closed a royalty financing agreement with Castle Creek Biosciences, a late-stage cell and gene therapy company, to support Castle Creek’s planned D-Fi (FCX-007) Phase 3 clinical study. D-Fi is an injectable autologous gene-modified cell therapy in development for the treatment of dystrophic epidermolysis bullosa (DEB), a devastating, painful, and debilitating rare genetic skin disorder. D-Fi has been granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA). Ligand led a $75 million investment in D-Fi by committing $50 million to the syndicated round. An additional $25 million was secured from a syndicate of co-investors. In return for the $75 million investment, investors will receive a high-single digit royalty which is shared on a pro-rated basis; therefore Ligand will net a mid-single digit royalty.

Portfolio Updates

On April 29, Verona announced Ohtuvayre net sales of $71.3 million for the first quarter 2025, representing an increase of 95% compared to the prior quarter. This growth was driven by significant increases in prescriptions, prescribers, new patients and refills.
On April 29, Travere and its European partner, CSL Vifor, announced that the European Commission approved the conversion of the conditional marketing approval into standard marketing authorization for Filspari for the treatment of adults with primary IgA nephropathy.
On April 26, UroGen announced encouraging safety data from its Phase 1 dose-escalation study for UGN-301 (zalifrelimab) intravesical solution, an investigational drug in development for the treatment of recurrent non-muscle

On April 24, Merck announced Capvaxive sales of $107 million for the first quarter of 2025, a 120% increase over the prior quarter. Merck reiterated that there has been continued uptake of Capvaxive since the product’s launch in the third quarter of 2024.

On April 11, Palvella announced Qtorin rapamycin 3.9% anhydrous gel for the treatment of microcystic lymphatic malformations (microcystic LMs) was featured by Dr. Amy Paller, a widely recognized key opinion leader in dermatology, in an oral presentation at the 15th World Congress of Pediatric Dermatology. In January, Palvella announced that the first patients were dosed in TOIVA, a multicenter, Phase 2 clinical trial designed to evaluate the safety and efficacy of Qtorin 3.9% rapamycin anhydrous gel for the treatment of cutaneous venous malformations (cutaneous VMs). In addition, in February Palvella announced that it will expand SELVA, the Phase 3 clinical trial of Qtorin 3.9% rapamycin anhydrous gel for the treatment of microcystic LMs, to include patients ages 3 to 5 years old. Previously, trial participants were required to be at least six years old.

On March 26, Merck, announced that the European Commission (EC) approved Capvaxive (pneumococcal 21-valent conjugate vaccine) for active immunization for the prevention of invasive disease and pneumonia in individuals 18 years of age and older. Capvaxive is a pneumococcal vaccine specifically designed to help protect adults from the serotypes responsible for the majority of invasive pneumococcal disease (IPD) cases. This decision authorizes the marketing of Capvaxive in all 27 European Union (EU) member states, as well as Iceland, Liechtenstein and Norway.
On March 17, Travere Therapeutics announced it has submitted a supplemental New Drug Application (sNDA) to the FDA seeking priority review for traditional approval of Filspari (sparsentan) for the treatment of focal segmental glomerulosclerosis (FSGS), a rare proteinuric kidney disorder in both children and adults. Travere expects to receive notice regarding the acceptance for review of the sNDA submission as well as the timeline for sNDA review from the FDA in the second quarter of 2025. Additionally, the FDA recently notified Travere that Risk Evaluation and Mitigation Strategy (REMS) monitoring for embryo-fetal toxicity is no longer necessary. Travere plans to submit a REMS modification. The FDA indicated that the amendment is not expected to impact the review timeline and Travere continues to expect a REMS modification target action date under the Prescription Drug User Act of August 28, 2025.

Adjusted Financial Measures

Ligand reports adjusted net income from continuing operations, adjusted net income per diluted share and adjusted earnings per diluted share in addition to, not as a substitute for, and does not consider such measures superior to, financial measures calculated in accordance with GAAP. The Company also reports a core calculation for each of the foregoing measures which excludes any realized gain from sales of Viking Therapeutics common stock. Additionally, adjusted earnings per diluted share is a key component of the financial metrics utilized by the Company’s board of directors to measure, in part, management’s performance and determine significant elements of management’s compensation. The Company’s financial measures under GAAP include share-based compensation expense, amortization of debt-related costs, amortization related to acquisitions and intangible 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, transaction costs, income tax effect of adjusted reconciling items and others that are listed in the itemized reconciliations between GAAP and non-GAAP adjusted financial measures included at the end of this press release. A reconciliation of forward-looking non-GAAP 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 adjusted earnings per diluted share, which we expect to have a significant impact on our future GAAP financial results.
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 (800) 715-9871 using the conference ID 3661098. International participants outside of Canada may use the toll number +1(646) 307-1963. To participate via live or replay webcast, a link is available at www.ligand.com.invasive bladder cancer.

On May 8, 2025 Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a clinical-stage biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, reported financial results for the first quarter ended March 31, 2025, and provided a business update (Press release, Janux Therapeutics, MAY 8, 2025, View Source [SID1234652749]).

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

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

                  Schedule Your 30 min Free Demo!

"We are proud to advance into the next phase of our clinical journey for JANX007 and begin treating patients in our Phase 1b expansion studies," said David Campbell, Ph.D., President and CEO of Janux. "We also look forward to our first R&D Day where we will unveil previously undisclosed preclinical programs that utilize our expertise and platform technologies to address significant unmet medical needs."

RECENT BUSINESS HIGHLIGHTS AND FUTURE MILESTONES:

•
Initiated first Phase 1b expansion study with JANX007 in taxane-naïve mCRPC patients.
In December 2024, Janux reported positive interim clinical data from the Phase 1a dose escalation portion of the trial in 16 metastatic castration-resistant prostate cancer (mCRPC) patients with a median of four prior lines of therapy. At that time, the median radiographic progression-free survival (rPFS) reported was 7.4 months for all 16 patients.* As of April 21, 2025, updated results** have been achieved in the same 16 patients supporting the initiation of the Phase 1b expansion studies:

•
Median rPFS of 7.5 months (n=16)
•
Median rPFS of 7.9 months for patients treated at 6mg and 9mg target doses (n=9)
•
6-month rPFS of 65% (n=16)
•
6-month rPFS of 78% for patients treated at 6mg and 9mg target doses (n=9)
•
Safety data remained consistent with the December 2024 data disclosure (n=16)
*8/16 patients were noted as in-progress in the December 2024 reported results.

**rPFS results based upon Kaplan-Meier estimate.

Janux selected 0.3/2/6mg and 0.3/2/9mg with dosing administered once weekly or once every two weeks as the two dose regimens for the Phase 1b expansion studies. In addition, Janux has selected a CRS-mitigation strategy to support the initiation of the Phase 1b expansion studies that is designed to reduce the risk of overuse of steroids while maintaining the early cycle grades 1 and 2 CRS profile reported in December.

•
Janux plans to initiate three additional Phase 1b expansion studies with JANX007, evaluating:

•
JANX007 in combination with an androgen receptor inhibitor (ARi) in taxane-experienced, ARi-naïve mCRPC patients
•
JANX007 monotherapy in PARP inhibitor-resistant mCRPC patients
•
JANX007 monotherapy in NHT- and taxane-experienced mCRPC patients designed to support OPTIMUS dose selection for registrational studies

•
JANX007 continues to enroll in the first-in-human Phase 1 clinical trial in mCRPC (NCT05519449).

•
JANX008 continues to enroll in the first-in-human Phase 1 clinical trial in advanced or metastatic solid tumors (NCT05783622).

Additional data from JANX007 and JANX008 will be presented at future Janux events in the second half of 2025. Separately, Janux will host an R&D Day in mid-2025 highlighting product candidates identified from its preclinical pipeline to move into clinical trials.

FIRST QUARTER 2025 FINANCIAL RESULTS:

•
Cash and cash equivalents and short-term investments: As of March 31, 2025, Janux reported cash and cash equivalents and short-term investments of $1.01 billion compared to $1.03 billion at December 31, 2024.

•
Research and development expenses: Research and development expenses for the quarter ended March 31, 2025, were $25.1 million compared to $14.1 million for the comparable period in 2024.

•
General and administrative expenses: General and administrative expenses for the quarter ended March 31, 2025, were $9.8 million compared to $7.3 million for the comparable period in 2024.

•
Net loss: For the quarter ended March 31, 2025, Janux reported a net loss of $23.5 million compared to a net loss of $14.8 million for the comparable period in 2024.

Janux’s TRACTr and TRACIr Pipeline

Janux’s first clinical candidate, JANX007, is a TRACTr that targets prostate-specific membrane antigen (PSMA) and is being investigated in a Phase 1 clinical trial in adult patients with mCRPC. Janux’s second clinical candidate, JANX008, is a TRACTr that targets epidermal growth factor receptor (EGFR) and is being studied in a Phase 1 clinical trial for the treatment of multiple solid cancers including colorectal carcinoma, squamous cell carcinoma of the head and neck, non-small cell lung cancer, renal cell carcinoma, small cell lung cancer, pancreatic ductal adenocarcinoma and triple-negative breast cancer. We are also generating a number of additional TRACTr and TRACIr programs for potential future development, some of which are at development candidate stage or later. We are currently assessing priorities in our preclinical pipeline.

On May 8, 2025 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a commercial biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported first quarter 2025 financial results and corporate updates (Press release, Iovance Biotherapeutics, MAY 8, 2025, View Source [SID1234652748]).

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

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

                  Schedule Your 30 min Free Demo!

Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "During the start of the new year, our first quarter revenue was impacted by a significant reduction in capacity during the annual scheduled maintenance at the Iovance Cell Therapy Center (iCTC). Since full production has now resumed at the iCTC, we now expect infusions to grow in the second quarter as compared to the first quarter. Additionally, based on our experience to date, we are revising full-year 2025 revenue guidance to reflect recent launch dynamics. In the first 12 months of our U.S. launch, we have executed toward our long-term adoption goals by treating more than 275 Amtagvi patients and generating more than $210 million in revenue. Beyond the U.S. launch, we are on track this year for potential Amtagvi regulatory approvals in three new ex-U.S. markets as well as a clinical data update from our registrational trial in non-small cell lung cancer."

First Quarter 2025 Financial Results, Corporate Guidance, and Updates

Product Revenue and Guidance

First Quarter 2025 Total Product Revenue: Iovance recognized total revenue of $49.3 million from sales of Amtagvi and Proleukin during the first quarter ended March 31, 2025.

1Q25 Amtagvi Revenue: Product revenue from U.S. Amtagvi sales was $43.6 million, impacted by a reduction in capacity during annual scheduled maintenance at the iCTC. Production has resumed enabling full capacity for infusions in the second quarter 2025. Iovance currently anticipates infusing between 100 and 110 commercial patients in the second quarter.
1Q25 Proleukin Revenue: Product revenue also included $5.7 million in Proleukin sales, primarily reflecting clinical and manufacturing use after stocking at major U.S. wholesalers in 2024. Significant orders are expected in the current quarter. Proleukin is used in the Amtagvi treatment regimen and other commercial, clinical, manufacturing, and research settings, which provide additional revenue.
Amtagvi Growth Potential at U.S. ATCs in 2025: As of today, Iovance’s treatment network of more than 80 ATCs includes an initial wave of 70 ATCs and more than 10 ATCs in process to become a second wave. Fifty-six ATCs completed tumor resections, 48 infused one or more patients, and 11 infused more than 10 patients. These trends highlight growing adoption and significant growth potential. Several new ATCs are expected to treat their first patients in the remaining weeks of the second quarter of 2025.
Full Year 2025 Total Product Revenue Guidance: Iovance is revising total product revenue guidance within the range of $250 to $300 million in the first full calendar year of Amtagvi sales. The updated forecast considers experience with ATC growth trajectories and treatment timelines for new ATCs. Beyond ATCs, large community practices are expected to expand market opportunity. Amtagvi adoption will accelerate in 2025 with broader utilization and higher demand. Proleukin sales are also expected to accelerate throughout the remainder of 2025 with restocking to U.S. distributors and sales growth to manufacturers and for other clinical and manufacturing uses. Iovance expects significant growth in total product revenue for full year 2026 and beyond. Gross margins are expected to increase over time and remain on track to surpass 70% over the next several years.
Full Year 2025 Expense Guidance and Cash Position: As of March 31, 2025, Iovance had cash, cash equivalents, investments, and restricted cash of approximately $366 million. The current cash position and anticipated product revenue are expected to be sufficient to fund current and planned operations, including manufacturing expansion, into the second half of 2026. Cash burn for full year 2025 is expected to remain in line with prior guidance of less than $300 million, with a strong focus on optimizing spending and reducing expenses throughout the organization, including flat operating expenses related to Amtagvi manufacturing headcount expansion for the latter half of 2025.
Macroeconomic and Geopolitical Trends: Iovance is well-positioned to operate in the current macroeconomic and geopolitical environment. Amtagvi manufacturing and intellectual property are fully located in the U.S., providing a strategic advantage within the biopharma industry. All of Iovance’s investigational TIL products are manufactured in the U.S.
Amtagvi (Lifileucel) U.S. Launch Highlights in Advanced Melanoma

The U.S. FDA approved Amtagvi (lifileucel) on February 16, 2024, as the first treatment option for patients with advanced melanoma after anti-PD-1 and targeted therapy. Amtagvi is the first FDA-approved T cell therapy for a solid tumor indication.
More than 80 U.S. ATCs have joined or are about to join our network across 35 states and 95% of addressable patients live within 200 miles of an ATC. Additional U.S. ATCs will be added steadily throughout 2025, focusing on quality ATCs with a high volume of eligible patients, including large community practice ATCs.
Community referral activities are accelerating rapidly throughout the U.S. to drive additional patient volume to the ATCs. Large community practices are currently onboarding, creating a new and significant opportunity for more patients to receive Amtagvi quickly after frontline therapy.
Manufacturing turnaround time is aligning with launch expectations of approximately 34 days from inbound to return shipment to ATCs. Iovance expects to shorten the manufacturing turnaround time in 2025. The overall commercial manufacturing experience remains consistent with prior clinical experience.
Amtagvi is a preferred second-line or subsequent therapy in the National Comprehensive Cancer Network guidelines for treatment of cutaneous melanoma.
Reimbursement remains successful, with an average financial clearance time of about three weeks.
Approximately 75% of Amtagvi patients are covered by private payers. To date, payers or plans covering more than 250 million lives have added Amtagvi to policies since its launch.
Launch Expansion into New Markets

Amtagvi has the potential to address more than 30,000 patients annually with previously treated advanced melanoma across the U.S. and initial global markets with significant populations of previously treated advanced melanoma patients.¹
Regulatory dossiers are under review, submitted, or planned across multiple international markets for lifileucel for the treatment of adult patients with unresectable or metastatic melanoma after anti-PD-1 and targeted therapy. If approved, lifileucel will be the first and only approved therapy in this treatment setting in all markets.
Amtagvi has the potential to be approved in three new markets in 2025, including the United Kingdom, Canada, and all EU member states. Recently, the iCTC and Iovance’s contract manufacturer successfully completed regulatory inspections by the European Medicines Agency.
Fifteen ATCs are targeted by year-end to support initial launch markets outside the U.S.
Named patient programs are planned outside the U.S. to provide early access to treatment prior to national reimbursement and are also expected to provide initial revenue from these markets.
Additional regulatory submissions remain on track for Australia in the first half of 2025 and Switzerland in the second half of 2025.
Recent Iovance TIL Cell Therapy Pipeline Highlights

Lifileucel in Frontline Advanced Melanoma
Strong momentum continues with global site activation and patient enrollment in the registrational TILVANCE-301 trial, which is intended to support U.S. approval of Amtagvi in combination with pembrolizumab in frontline advanced melanoma, and full approval in post-anti-PD-1 melanoma.
Cohort 1D in the IOV-COM-202 trial is investigating lifileucel in combination with nivolumab and relatlimab in frontline advanced melanoma.
Lifileucel in Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC)
Iovance remains on track to share additional data in the second half of 2025 from the IOV-LUN-202 registrational Phase 2 trial in post-anti-PD-1 NSCLC.
The IOV-LUN-202 trial is intended to support a potential accelerated approval of lifileucel in post-anti-PD-1 NSCLC in the U.S., with an anticipated regulatory decision in 2027. The FDA previously provided positive regulatory feedback on the proposed potency matrix in NSCLC and the IOV-LUN-202 clinical trial design.
Lifileucel in Frontline Advanced NSCLC
Iovance is pursuing a frontline therapy strategy to integrate lifileucel plus pembrolizumab following chemotherapy for patients with EGFR wild type NSCLC, representing most patients with an unmet medical need in this setting.
Cohorts 3D and 3E in IOV-COM-202 trial are investigating this regimen to inform a registrational and confirmatory trial design in frontline advanced NSCLC.
Lifileucel in Endometrial Cancer
Iovance is actively enrolling in the IOV-END-201 Phase 2 trial for advanced endometrial cancer, with initial results expected in the second half of 2025. The trial is investigating lifileucel after platinum-based chemotherapy and anti-PD-1 therapy regardless of mismatch repair (MMR) status, which represents a significant unmet medical need.
Next Generation TIL Pipeline
PD-1 Inactivated TIL Cell Therapy (IOV-4001): The Phase 2 efficacy portion of the IOV-GM1-201 trial continues to enroll patients to evaluate IOV-4001 in previously treated advanced melanoma and NSCLC. Iovance utilizes the TALEN technology licensed from Cellectis to develop IOV-4001 and other investigational gene-edited TIL cell therapies with multiple knockout targets to potentially improve efficacy.
Next Generation Interleukin-2 (IL-2) for TIL Treatment Regimen (IOV-3001): A Phase 1/2 clinical trial, IOV-IL2-101, is enrolling patients to investigate IOV-3001, a second-generation, modified IL-2 analog for use in the TIL therapy treatment regimen. Preclinical studies of IOV-3001 demonstrated the potential for improved safety with strong effector T cell expansion.
Next Generation, Cytokine-Tethered TIL Therapy (IOV-5001): IND-enabling studies are proceeding as planned for IOV-5001, a genetically engineered, inducible, and tethered interleukin-12 (IL-12) TIL cell therapy, in support of an IND in 2025 for clinical development for multiple indications.
Manufacturing Capacity Expansion

Iovance’s U.S.-based manufacturing network, consisting of the iCTC and an FDA-approved contract manufacturer, supplies clinical and commercial TIL cell therapies to patients globally.
The iCTC facility, representing the bulk of Amtagvi and clinical TIL product production, completed annual scheduled maintenance and successfully restarted full production.
The Iovance manufacturing network currently has staffed capacity for more than 1,300 patients annually and is built to serve several thousand patients annually with commercial Amtagvi and for clinical trials across North America, Europe and Asia Pacific. Expansion is currently underway at the iCTC facility to supply TIL cell therapies to more than 5,000 patients annually in the next few years, with additional expansion opportunities also in development.
Corporate Updates

Iovance currently owns approximately 280 granted or allowed U.S. and international patents and patent rights for Amtagvi and other TIL-related technologies that are expected to provide exclusivity through at least 2042. This patent portfolio covers TIL compositions and methods of treatment and manufacturing in a broad range of cancers, with Gen 2 patent rights expected to provide exclusivity for Amtagvi into 2038 and additional patent rights, including methods of treating melanoma and compositions and methods for potency assays, expected to provide exclusivity into 2039 and 2042, respectively. Iovance also owns an industry-leading patent portfolio covering TIL products produced with genetic engineering, using core biopsies and peripheral blood as starting material, and using combinations of TIL products with checkpoint inhibitors, as well as Iovance’s proprietary IovanceCares system. More information on Iovance’s patent portfolio is available on the Intellectual Property page on www.iovance.com.
First Quarter 2025 Financial Results

As of March 31, 2025, Iovance’s cash position is approximately $366 million. The current cash position and anticipated product revenue are expected to be sufficient to fund current and planned operations into the second half of 2026.

Net loss for the first quarter of 2025 was $116.2 million, or $0.36 per share, compared to a net loss of $113.0 million, or $0.42 per share, for the first quarter of 2024.

Revenue was $49.3 million for the first quarter of 2025 and consisted of product revenue from Amtagvi and Proleukin sales. Iovance recognized $43.6 million in revenue from Amtagvi infusions that were completed during the first quarter of 2025 and $5.7 million in global revenue for Proleukin. Revenue for the first quarter of 2024 was $0.7 million for global sales of Proleukin.

The increase in revenue in the first quarter 2025 over the prior year period was primarily attributable to the U.S. launch of Amtagvi, including revenue recognized for Amtagvi, as well as Proleukin revenue in the U.S.

Cost of sales includes inventory, overhead and related cash and non-cash expenses that are directly associated with sales of Amtagvi and Proleukin, as well as manufacturing costs for Amtagvi. Cost of sales for the first quarter 2025 was $49.7 million, which included $15.0 million for period costs associated with patient drop off and manufacturing success rates, $5.4 million for non-cash amortization expense for intangible assets and fair value mark up of inventory, and $1.3 million in royalties payable on product sales. For the first quarter 2024, cost of sales of $7.3 million was primarily related to non-cash amortization for intangible assets.

Increases in cost of sales in the first quarter over the prior year period were primarily attributable to costs associated with the initiation and growth of product sales, certain costs associated with patient drop off and manufacturing success rates, and related cash and non-cash expenses tied to the U.S. launch of Amtagvi that began during the first quarter of 2024.

Research and development expenses were $76.9 million for the first quarter of 2025, a decrease of 4% compared to $79.8 million for the first quarter of 2024. The decreases in research and development expenses in the first quarter 2025 over the prior year period were primarily attributable to the transition of Amtagvi to commercial manufacturing. This decrease was partially offset by higher headcount and related costs, including stock-based compensation, and clinical trial costs resulting from continued enrollment in existing trials.

Selling, general and administrative expenses were $43.9 million for the first quarter of 2025, an increase of 40% compared to $31.4 million for the first quarter of 2024. The increase in selling, general and administrative expenses in the first quarter compared to the prior year period was primarily attributable to increases in headcount and related costs, including stock-based compensation, to support the growth in the overall business and related corporate infrastructure, as well as marketing and legal costs and costs incurred to support the commercialization of Amtagvi and Proleukin.

For additional information, please see the Company’s Selected Consolidated Balance Sheets and Statements of Operations below.

Webcast and Conference Call

Management will host a conference call and live audio webcast to discuss these results and provide a corporate update today at 4:30 p.m. ET. To listen to the live or archived audio webcast, please register at View Source The live and archived webcast can be accessed in the Investors section of the Company’s website, IR.Iovance.com, for one year.

1. World Health Organization International Agency for Research on Cancer (IARC) GLOBOCAN 2022.