On August 13, 2025 OncoBeta GmbH, a medical device company specialising in innovative epidermal radioisotope therapies, reported 12-months interim results from its international Phase IV, multi-centre clinical trial evaluating the efficacy and safety of Rhenium-SCT (Skin Cancer Therapy) in patients with non-melanoma skin cancer (NMSC) (Press release, OncoBeta, AUG 13, 2025, View Source [SID1234655217]).

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The EPIC-Skin Study (Efficacy of Personalised Irradiation with Rhenium-SCT for the Treatment of Non-Melanoma Skin Cancer) is designed to assess treatment efficacy and safety, as well as key patient-reported outcomes including quality of life, treatment comfort, and cosmetic results.1 The study is based on the clinically validated effect of the beta-emitter rhenium-188 in treating basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).2

Treatment data is available for 184 adult patients (with 254 lesions) across 7 study centres in Australia, Austria, Germany, the United Kingdom, and South Africa. All participants had histologically confirmed stage I or II NMSC. The median patient age was 70.3 years (range 27–95 years), and 53.3% of participants were male. Patients had one (71.2%), two (19.6%), or three (9.2%) lesions treated, which were located on the head & neck (11.8%), trunk (11.8%), lower limbs (11.8%), or upper limbs (9.1%).1

Treatment & Methodology

Rhenium-SCT was administered as a single 50-Gy topical dose of rhenium-188 embedded in a resin applied via adhesive film to the lesion site. Efficacy was assessed using modified RECIST criteria, at 12 months follow-up. Quality of life was assessed using the Skin Cancer Index (SCI) at baseline, 6 months, and 12 months. Treatment comfort was assessed using a patient questionnaire, whilst patient- and clinician-evaluated cosmetic outcomes were determined using a visual analogue scale (VAS) grading of 0-10 (0 = very poor; 10 = no wound detectable). Safety was assessed via treatment-emergent adverse events (TEAEs) and CTCAE (Common Terminology Criteria for Adverse Events) grading.

Key 12-Month Results:1

Overall response rate: 97.3%
Complete response rate: 94.1%
Partial response rate: 3.2%
Mean improvement in quality of life: +10.55 points from baseline
Pain/discomfort during treatment: None reported
Cosmetic outcomes: Favourable results reported by both patients and clinicians
Most common toxicity (12-month): Grade 1 hypopigmentation (60.4%)
No CTCAE toxicities above Grade 2 observed at 12 months
These findings confirm that Rhenium-SCT, administered in a single session, delivers sustained high efficacy and improved quality of life, with excellent cosmetic outcomes and minimal adverse effects.

"Rhenium-SCT has consistently demonstrated effectiveness and safety in prior studies," said Dr. Gerhard Dahlhoff, Medical Director at OncoBeta. "This 12-month interim data further reinforces its value as a non-invasive, targeted treatment option for NMSC, particularly for patients seeking alternatives to surgery due to cosmetic or health-related concerns."

"The 12-month results from the EPIC-Skin Study represent a major milestone for OncoBeta," added Shannon D. Brown III, CCO OncoBeta & Managing Director Europe. "These results support the efficacy, safety, and patient satisfaction associated with Rhenium-SCT. These are the three foundational pillars of our patient-first vision, emphasising not only clinical outcomes, but also the patient experience in achieving them."

About the Rhenium-SCT (Skin Cancer Therapy)
Non-melanoma skin cancer (NMSC) is the most common form of cancer in humans.3 The most common cause of NMSC is sun exposure, while other predisposing factors include genetic skin conditions and immunosuppressive diseases or treatments.4
The Rhenium-SCT is a painless*, non-invasive‡ therapy that provides aesthetic results, even in cases otherwise considered difficult to treat.1,5,6 The Rhenium-SCT utilises the radioisotope Rhenium-188 in an epidermal application with optimal properties for the treatment of NMSCs (non-melanoma skin cancers). The Rhenium-SCT is a precise, personalised therapy2 that is only applied to the area needed to treat without affecting the healthy tissue. The specially designed device ensures the Rhenium-SCT compound never comes in direct contact with the patient’s skin and the application is safe and simple for the applying physician. Scar-free healing of the treated lesion area and the regeneration of healthy tissue occurs usually within a few weeks after treatment.

On August 12, 2025 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the second quarter 2025 and provided a business update for its oncology clinical programs CB-010 and CB-011 with data disclosures on track for H2 2025 (Press release, Caribou Biosciences, AUG 12, 2025, View Source [SID1234655130]).

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"Caribou is advancing allogeneic CAR-T cell programs to deliver off-the-shelf therapies designed for rapid treatment and broad patient access," said Rachel Haurwitz, PhD, Caribou’s president and CEO. "Our clinical programs, CB-010 for large B cell lymphoma and CB-011 for multiple myeloma, continue to generate encouraging Phase 1 results, reinforcing our conviction in the potential of these therapies. We remain on track to report robust datasets from both programs this year, which we expect to provide meaningful insights into the potential of our approach and the future of allogeneic CAR-T cell therapies."
Clinical highlights
CB-010, a clinical-stage allogeneic anti-CD19 CAR-T cell therapy for B cell non-Hodgkin lymphoma
•Caribou completed enrollment of the 20-patient confirmatory cohort using the Company’s partial HLA matching strategy in the ANTLER Phase 1 clinical trial for patients with second-line large B cell lymphoma (2L LBCL).
•To date, data continue to demonstrate that a single dose of CB-010 has the potential to drive outcomes that are on par with the safety, efficacy, and durability of approved autologous CAR-T cell therapies.

CB-011, a clinical-stage allogeneic anti-BCMA CAR-T cell therapy for multiple myeloma
•Caribou completed planned enrollment for the dose escalation portion of the CaMMouflage Phase 1 clinical trial for patients with relapsed or refractory multiple myeloma (r/r MM).
•Caribou continues to observe encouraging efficacy in patients treated with CB-011 at multiple active dose levels.

2025 anticipated milestones
•CB-010 ANTLER: Caribou plans to present data from both the additional 2L and prior CD19 relapsed LBCL patient cohorts in H2 2025 and is interacting with the FDA on a potential pivotal trial to be initiated following alignment. This update is expected to include:
▪Initial safety and efficacy data on the confirmatory cohort (20 patients) with partial HLA matching, with a minimum of six months of follow up for the majority of patients, as well as an update on the larger, maturing dataset presented previously.
▪Pivotal trial design and timeline, contingent on positive data and FDA alignment.
•CB-011 CaMMouflage: Caribou plans to present dose escalation data from its ongoing CaMMouflage Phase 1 clinical trial in r/r MM in H2 2025. This update is expected to include:

▪Initial safety and efficacy data on a minimum of 25 patients at multiple dose levels using the deeper lymphodepletion regimen with at least three months of follow up.
▪Recommended dose(s) for expansion and plans for dose expansion.
Second quarter 2025 financial results
Cash, cash equivalents, and marketable securities: Caribou had $183.9 million in cash, cash equivalents, and marketable securities as of June 30, 2025, compared to $249.4 million as of December 31, 2024. Caribou expects its cash, cash equivalents, and marketable securities will be sufficient to fund its current operating plan into H2 2027.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $2.7 million for the three months ended June 30, 2025, compared to $3.5 million for the same period in 2024.

R&D expenses: Research and development expenses were $27.7 million for the three months ended June 30, 2025, compared to $35.5 million for the same period in 2024. The decrease was primarily related to the previously announced strategic pipeline prioritization and related workforce reduction and lower costs associated with the ongoing CB-010 ANTLER and CB-011 CaMMouflage Phase 1 clinical trials.

G&A expenses: General and administrative expenses were $10.4 million for the three months ended June 30, 2025, compared to $11.5 million for the same period in 2024. The decrease was primarily due to reduced personnel-related expenses, including stock-based compensation, related to the previously announced strategic pipeline prioritization and related workforce reduction, lower patent prosecution and maintenance costs, and lower legal and other service related expenses. The decrease was partially offset by an increase in other facilities and allocated expenses.

Non-recurring, non-cash impairment charges: Non-recurring, non-cash impairment charges were $21.3 million for the three months ended June 30, 2025, and include charges related to the previously announced strategic pipeline prioritization and an impairment of the Company’s stock investment in a private company.

GAAP and non-GAAP net loss and net loss per share, basic and diluted: Caribou reported a net loss of $54.1 million, or $0.58 per share, basic and diluted, for the three months ended June 30, 2025, compared to $37.7 million, or $0.42 per share, basic and diluted, for the same period in 2024. Non-GAAP net loss for the three months ended June 30, 2025, excluding $21.3 million of non-cash impairment charges, was $32.8M, or $0.35 per share, basic and diluted.

About CB-010
CB-010 is an allogeneic anti-CD19 CAR-T cell therapy being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) in the ongoing ANTLER Phase 1 clinical trial. To Caribou’s knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to enhance CAR-T cell activity by limiting premature CAR-T cell exhaustion. The FDA granted CB-010 Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug, and Fast Track designations for B-NHL. Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

About CB-011
CB-011 is an allogeneic anti-BCMA CAR-T cell therapy being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. To Caribou’s knowledge, CB-011 is the first allogeneic CAR-T cell therapy in the clinic that is engineered to enable activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track and Orphan Drug designations by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

On August 12, 2025 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel allogeneic, or "off the shelf", cell therapies for serious neurological and ophthalmic conditions, reported its second quarter 2025 financial and operating results and will host a conference call today at 4:30 p.m. Eastern Time to discuss these results and provide a business update (Press release, Lineage Cell Therapeutics, AUG 12, 2025, View Source [SID1234655157]).

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"Following the recent positive 36-month clinical data update with the OpRegen RPE cell therapy program, which is licensed by Genentech and Roche, we continue to remain confident in its potential to address a significant medical need, especially because long term clinical outcomes following a single administration of OpRegen cell therapy are challenging the long-held view that GA is an irreversible condition," stated Brian M. Culley, Lineage CEO. "It is notable that among patients who received extensive one-time coverage of OpRegen RPE cells across the area of atrophy, anatomical and functional benefits have lasted for at least three years, outcomes consistent with meaningful disease stabilization and even improvement."

"In addition to supporting our partners in advancing the OpRegen program, we are equally excited to have reached a milestone with our OPC1 program for the treatment of spinal cord injury, treating our first-ever chronic patient with a new parenchymal spinal delivery system. We also solidified our position as a leader in allogeneic cell process development and manufacturing by reporting in-house GMP production for each of two separate cell-based product candidates from a master and working cell bank system which, in its current form, can support a production capability of several million doses for a single-administration product. This is in addition to continuing to advance our ReSonanceTM program for the treatment of sensorineural hearing loss and evaluating other strategically selected early-stage initiatives. As our cell therapy platforms gain further validation, we believe our pipeline and cell manufacturing and related expertise continue to position us as a compelling partner and investment opportunity," added Mr. Culley.

Select Business Highlights

RG6501 (OpRegen Cell Therapy)
Positive RG6501 (OpRegen) Phase 1/2a Clinical Study 36 Month Results featured at Clinical Trials at the Summit (CTS) 2025. 2025 CTS highlights:
Gains in Best Corrected Visual Acuity (BCVA) in patients in Cohort 4 (less advanced GA) measured at month 12 remain evident through month 36 following subretinal administration of OpRegen cell therapy;
Mean change in BCVA among treated eyes for patients (n=10) completing 3-year follow up was +6.2 letters (compared to +5.5 letters at 24 months) (Early Treatment Diabetic Retinopathy Study (ETDRS) assessment);
Improvement in BCVA and outer retinal structure in patients with extensive OpRegen bleb coverage of their GA area was greater than in patients with limited coverage and persisted through month 36
Effects were greater on average in the five (5) patients with extensive OpRegen cell therapy coverage of atrophic areas at the time of surgical delivery
In these patients’ treated eyes, the mean change in BCVA was +9.0 ETDRS letters for those completing 3-year follow-up (compared to +7.4 ETDRS letters at 24 months) (n=5)
These data suggest that OpRegen cell therapy may counteract RPE cell dysfunction and loss in GA by providing support to the remaining retinal cells within atrophic areas, and these effects appear durable through at least 36 months after a single administration

Ongoing execution of Lineage’s contributions to its collaboration with Roche and Genentech across multiple functional areas, including support for the ongoing Phase 2a clinical study (the "GAlette Study") in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) at sites in the U.S. and Israel.
In addition to testing of other surgical parameters, Genentech currently plans to evaluate two proprietary surgical delivery devices that have potential advantages over available off-the-shelf devices in the GAlette Study.

Ongoing efforts to further support development of OpRegen RPE cell therapy under a separate services agreement with Genentech, signed May 2024, including: (i) activities to support the ongoing Phase 1/2a study long term follow-up and the currently enrolling Phase 2a GAlette Study; and (ii) additional technical training and materials related to our cell therapy technology platform to support commercial manufacturing strategies.

Manufacturing Capability
Successfully completed a production run for two different product candidates, each produced from a customized, two-tiered current Good Manufacturing Practice ("cGMP") cell banking system, highlighting the application of the Lineage platform across multiple programs.
This production process utilizes a genetically-stable master cell bank created from a single, well-characterized pluripotent cell line, to generate a working cell bank, which then provides the source material for a final cell-based product candidate.
This demonstrated cGMP production process should enable the ability to produce millions of doses of a cost-effective, scalable and consistent supply of an allogeneic, cell-based product derived from a single initial cell line, that can be applied across multiple programs.

OPC1
First chronic spinal cord injury patient treated in the DOSED (Delivery of Oligodendrocyte Progenitor Cells for Spinal Cord Injury: Evaluation of a Novel Device) clinical study.
First chronic SCI patient treated in DOSED was a neurologically complete SCI injury (American Spinal Injury Association Impairment Scale [AIS] grade A), with a single neurological level of injury (NLI) from levels T1 to T10, and the novel delivery system successfully administered a one-time injection of OPC1.
Hosted the 3rd Annual Spinal Cord Injury Investor Symposium (3rd SCIIS) in partnership with the Christopher & Dana Reeve Foundation.
Balance Sheet Highlights

Cash, cash equivalents, and marketable securities of $42.3 million as of June 30, 2025, is expected to support planned operations into Q1 2027.

Second Quarter Operating Results

Revenues: Revenue is generated primarily from collaboration revenues, royalties, and other revenues. Total revenues for the three months ended June 30, 2025 were $2.8 million, a net increase of $1.4 million as compared to $1.4 million for the same period in 2024. The increase was primarily driven by more collaboration revenue recognized from deferred revenues under the Roche Agreement, as well as deferred revenues recognized upon termination of the VAC platform-related collaboration agreement.

Operating Expenses: Operating expenses are comprised of research and development ("R&D") expenses and general and administrative ("G&A") expenses. Total operating expenses for the three months ended June 30, 2025 were $22.5 million, an increase of $15.2 million as compared to $7.3 million for the same period in 2024. The overall increase was driven by the $14.8 million expense recognized for the loss on impairment for the intangible asset related to the VAC platform.

R&D Expenses: R&D expenses for the three months ended June 30, 2025 were $3.1 million, an increase of $0.2 million as compared to $2.9 million for the same period in 2024. The net increase was primarily driven by ongoing activities within our preclinical programs.

G&A Expenses: G&A expenses for the three months ended June 30, 2025 were $4.6 million, an increase of $0.2 million as compared to $4.4 million for the same period in 2024. The net increase was primarily driven by more costs incurred for services provided by third parties.

Loss from Operations: Loss from operations for the three months ended June 30, 2025 were $19.8 million, an increase of $13.9 million as compared to $5.9 million for the same period in 2024. This increase in loss was primarily driven by the impairment expense related to the VAC platform of $14.8 million, which is a non-recurring transaction.

Other Income/(Expenses): Other income/(expenses) for the three months ended June 30, 2025 reflected other expense of $10.6 million, compared to other income of $0.1 million for the same period in 2024. The net change was primarily attributable to the quarterly fair value remeasurement of the warrant liabilities of $12.7 million primarily due to an increase in our share price as compared to the prior quarter, partially offset by $1.7 million for exchange rate fluctuations related to Lineage’s international subsidiaries.

Net Loss Attributable to Lineage: The net loss attributable to Lineage for the three months ended June 30, 2025 was $30.5 million, or $0.13 per share (basic and diluted), compared to a net loss of $5.8 million, or $0.03 per share (basic and diluted), for the same period in 2024. The change was primarily driven by the loss on impairment expense related to a 2019 acquisition and the quarterly fair value remeasurement of the warrant liabilities.

Conference Call and Webcast

Interested parties may access the conference call on August 12, 2025, by dialing (800) 715-9871 from the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through August 19th, 2025, by dialing (800) 770-2030 from the U.S. and Canada and entering conference ID number 7788342.

On August 12, 2025 Citius Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR), a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, reported financial results for its fiscal third quarter ended June 30, 2025, and provided a business update (Press release, Citius Pharmaceuticals, AUG 12, 2025, View Source [SID1234655131]).

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"During the third quarter, Citius advanced its strategic priorities, and we believe we are now operationally positioned to transition from a development-stage enterprise to a fully integrated commercial organization. Final preparations are underway by our oncology subsidiary for the planned U.S. launch of LYMPHIR in the fourth quarter of 2025," said Leonard Mazur, Chairman and CEO of Citius Pharmaceuticals.

"In June 2025, we completed a $6 million registered direct offering, with the potential for an additional $9.8 million upon full warrant exercise, to fund commercialization activities and corporate operations. In July 2025, Citius Oncology further strengthened its capital position with $9 million in gross proceeds from a public offering. These financings, any proceeds we might receive from exercise of the June 2025 warrants and other capital raising activities during the quarter, together with the completion of major launch-enabling activities including commercial-scale manufacturing, labeling, packaging, and distribution services agreements with leading specialty pharmaceutical partners indicate we are well-prepared to deliver LYMPHIR to patients with cutaneous T-cell lymphoma, an underserved population in need of new treatment options. At the same time, we remain focused on advancing Mino-Lok and continue to engage with the U.S. Food and Drug Administration as we evaluate the best path forward for this potentially transformative antibiotic lock solutions for patients with catheter-related bloodstream infections," added Mazur.

FISCAL THIRD QUARTER 2025 Financial Results:

· R&D expenses were $1.6 million for the quarter ended June 30, 2025, compared to $2.8 million for the quarter ended June 30, 2024;

· G&A expenses were $4.4 million for the quarter ended June 30, 2025, as compared to $4.8 million for the quarter ended June 30, 2024;

· Stock-based compensation expense was $2.7 million for the quarter ended June 30, 2025, as compared to $3.1 million for the quarter ended June 30, 2024;

· Net loss was $9.2 million, or ($0.80) per share, for the quarter ended June 30, 2025, as compared to a net loss of $10.6 million, or ($1.57) per share, for the quarter ended June 30, 2024, as adjusted for the reverse stock split;

· At June 30, 2025, Citius Pharma had cash and cash equivalents of $6.1 million available to fund its operations. During the nine months ended June 30, 2025, the Company received net proceeds of $16.5 million from the issuance of equity and $1 million from the issuance of a note payable; and,

· On July 17, 2025, Citius Oncology completed a public offering generating net proceeds of approximately $7.4 million, after deducting placement agent fees and other offering expenses.

On August 12, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a late-stage clinical company advancing next-generation CAR T-cell therapies for patients with cancer, reported financial results and business highlights for the second quarter ended June 30, 2025 (Press release, Lyell Immunopharma, AUG 12, 2025, View Source [SID1234655158]). Lyell’s lead clinical program, LYL314, is a next-generation autologous dual-targeting CD19/CD20 CAR T-cell product candidate under evaluation in PiNACLE, a single-arm pivotal trial enrolling patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) in the 3L+ setting and in a Phase 1/2 study in the 2L setting.

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"Based on the high rate of durable complete responses achieved by LYL314 in patients with aggressive LBCL presented at the International Conference on Malignant Lymphoma in Lugano, Switzerland, in June, we believe that our CD19/CD20 CAR T-cell therapy will disrupt the therapeutic landscape by delivering meaningfully increased complete response rates and improved durability over the currently approved CD19 CAR T-cell therapies," said Lynn Seely, M.D., President and CEO of Lyell. "Our recent private placement with well-respected investors significantly derisks our business, extends our cash runway into mid-2027 and enables us to focus on rapidly advancing the clinical development of LYL314. We have initiated the PiNACLE single-arm pivotal trial for patients with LBCL receiving treatment in the third- or later-line setting and are on track to begin a second pivotal trial of LYL314 for patients with LBCL in the second-line setting by early 2026."

Second Quarter Updates and Recent Business Highlights

Lyell is advancing a pipeline of next-generation CAR T-cell product candidates targeting cancers with large unmet need and substantial patient populations. Its lead program, LYL314, is in pivotal development for patients with R/R LBCL and its preclinical programs target solid tumor indications.

LYL314: A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to approved CD19‑targeted CAR T-cell therapies for the treatment of LBCL

LYL314 is an autologous CAR T-cell product candidate with a true ‘OR’ logic gate to target B cells that express either CD19 or CD20 with full potency and that is manufactured with a process that enriches for CD62L-positive cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity. Following a successful End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA), LYL314 is currently being evaluated in the pivotal PiNACLE trial, which is a seamless expansion of the 3L+ cohort of the Phase 1/2 trial of patients with R/R LBCL. The Phase 1/2 trial continues to enroll CAR T-cell therapy naïve patients receiving treatment in the 2L setting and a pivotal trial for these 2L patients is expected be initiated by early 2026. The FDA has granted LYL314 Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for the treatment of R/R diffuse LBCL in the 3L+ setting. RMAT provides all the benefits of the Fast Track and Breakthrough Therapy designation programs and enables increased frequency of communications with the FDA on the development of LYL314.

PiNACLE is a single-arm pivotal trial evaluating LYL314 at a dose of 100 x 106 CAR T cells in patients with LBCL receiving treatment in the 3L+ setting. The trial is expected to enroll approximately 120 patients with R/R diffuse large B-cell lymphoma, high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed follicular lymphoma or Grade 3B follicular lymphoma who have not previously received CAR T-cell therapy. Patients may be treated with LYL314 in either the inpatient or outpatient setting and there is no upper age limit for eligibility. The primary endpoint of the trial is the overall response rate, including an evaluation of duration of response.
New clinical data from the Phase 1/2 multi-center clinical trial of LYL314 in patients with R/R LBCL were presented at the 18th International Conference on Malignant Lymphoma in June and included more mature data from patients treated in the 3L+ setting and initial data from patients treated in the 2L setting. The data were presented in an oral presentation titled "LYL314, a CD19/CD20 CAR T‑cell candidate enriched for CD62L+ stem-like cells, achieves high rates of durable complete responses in relapsed and/or refractory large B-cell lymphoma". Highlights include:
Fifty-one CAR T-naive patients with R/R LBCL received LYL314 as of April 15, 2025 (the data cutoff date for the presentation). The efficacy evaluable population consisted of 36 patients with Day 84 assessments or prior disease progression or death. Patient demographics and baseline disease characteristics were consistent with high-risk patient populations: median ages of 65 and 69 years in the 3L+ and 2L, respectively, 41% of 3L+ and 65% of 2L patients had Stage IV disease at trial entry, and 47% of 3L+ and 82% of 2L patients had primary refractory disease.
In efficacy-evaluable 3L+ patients, with a median follow-up of 9 months (N = 25): The overall response rate was 88% (22/25 patients), with 72% (18/25) of patients achieving a complete response. 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months.
In initial data from efficacy-evaluable 2L patients, with a median follow-up of 5 months (N = 11): The overall response rate was 91% (10/11 patients), with 64% (7/11) achieving a complete response. 100% (7/7) of patients with complete response were in complete response at their last assessment, including 3/3 patients at ≥ 6 months. In patients with primary refractory disease, a difficult to treat population, 70% (7/10) achieved a complete response.
In 51 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade ≥ 3 and low rates of Grade 1 (22%) or Grade 2 (35%) cytokine release syndrome (CRS) were reported. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 6% (Grade 1), 2% (Grade 2), and 14% (Grade ≥ 3) of patients. The median time to complete resolution of all reports of ICANS was 5 days, with rapid improvement (median of 2 days) to Grade 2 or lower with standard therapy. No deaths were related to LYL314 administration. LYL314 demonstrated robust expansion with ​a time to peak of 10 days.​ The final drug product contained the desired CD62L-positive naïve T-cell phenotype (median, 95%). Rapid and durable depletion of B cells was demonstrated through month 6 and up to the month 12 assessment.
An update on the progress of the PiNACLE trial is planned for late 2025. Data from this trial is expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting.
More mature data from the ongoing Phase 1/2 trial in the 2L setting are expected to be presented in late 2025.
A Phase 3 randomized controlled trial of LYL314 is expected to be initiated by early 2026 in patients receiving treatment in the 2L setting with R/R LBCL.

Preclinical Pipeline, Technologies and Manufacturing Protocols

Lyell is advancing next-generation fully-armed CAR T-cell product candidates, each including multiple technologies, designed to overcome T-cell exhaustion and lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment.

The first IND for a fully-armed CAR T-cell product candidate with an undisclosed target for solid tumors is expected in 2026.

Corporate Updates

In July, Lyell entered into a securities purchase agreement for a private placement with certain institutional and other accredited investors, for gross proceeds of up to approximately $100 million. The initial closing of approximately $50 million of common stock at a price of $13.32 per share occurred on July 25, 2025.
After deducting offering expenses, Lyell expects to use net proceeds from the private placement, together with its existing cash, cash equivalents, and marketable securities, to advance two pivotal-stage clinical trials of LYL314 as well as working capital for other general corporate purposes.

Second Quarter 2025 Financial Results

Lyell reported a net loss of $42.7 million for the second quarter ended June 30, 2025, compared to a net loss of $45.8 million for the same period in 2024. The $3.1 million decrease in net loss was primarily due to a decrease of $3.3 million in stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards. Non‑GAAP net loss, which excludes 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, decreased to $37.8 million for the second quarter ended June 30, 2025, compared to $39.1 million for the same period in 2024, primarily due to lower interest income primarily driven by decreased interest rates in 2025 coupled with lower cash equivalent and marketable securities balances.

GAAP and Non-GAAP Operating Expenses

Research and development (R&D) expenses were $34.9 million for the second quarter ended June 30, 2025, compared to $40.3 million for the same period in 2024. The decrease in second quarter 2025 R&D expenses of $5.4 million was primarily due to a $2.9 million reduction in research activities, collaborations and outside services due primarily to a reduction in costs associated with research and laboratory supplies and collaboration agreements and a $2.4 million decrease in personnel‑related expenses primarily due to reduced stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards. 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 second quarter ended June 30, 2025 were $32.6 million, compared to $37.2 million for the same period in 2024.
General and administrative (G&A) expenses were $9.8 million for the second quarter ended June 30, 2025, compared to $12.3 million for the same period in 2024. The decrease in second quarter 2025 G&A expenses of $2.5 million was primarily due to a $1.7 million decrease in stock-based compensation expense primarily related to a decrease in the value of new awards granted and a $0.8 million decrease in outside services primarily due to a reduction in legal expenses. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the second quarter ended June 30, 2025 were $7.1 million, compared to $7.8 million for the same period in 2024.
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 June 30, 2025 were approximately $297 million, compared to approximately $384 million as of December 31, 2024. Lyell believes that its cash, cash equivalents and marketable securities balances totaling approximately $347 million inclusive of the initial $50 million of proceeds from its recent private placement, will be sufficient to meet working capital and capital expenditure needs into mid-2027.