On October 31, 2023 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the company’s Phase 1 clinical trial of XMT-2056 (Press release, Mersana Therapeutics, OCT 31, 2023, View Source [SID1234636539]). XMT-2056 is a systemically administered Immunosynthen STING-agonist ADC that is designed to target a novel human epidermal growth factor receptor 2 (HER2) epitope and locally activate STING signaling in both tumor-resident immune cells and in tumor cells, providing the potential to treat patients with HER2-high or -low tumors as monotherapy and in combination with standard-of-care agents.

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"An in-depth analysis of cytokine, pharmacokinetic and other clinical data from patients enrolled in our Phase 1 trial indicated that XMT-2056 is a highly potent innate immune agonist," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "Based on these data and with patient safety at the forefront of our efforts, we have lowered the starting dose in our Phase 1 dose escalation design. We are pleased to have aligned with FDA on the path forward and are excited to have the opportunity to continue to investigate the potential of XMT-2056 and our Immunosynthen ADC platform in the clinic."

The multicenter Phase 1 open-label trial is investigating XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal and non-small-cell lung cancers. The dose escalation and dose expansion portions of the trial will evaluate and characterize the relationship of safety, tolerability and exposure of XMT-2056 and this candidate’s preliminary anti-tumor activity, as measured by overall response rate, duration of response and disease control rate.

The FDA has granted orphan drug designation to XMT-2056 for the treatment of gastric cancer. In August 2022, Mersana entered into a global collaboration providing GSK plc with an exclusive option to co-develop and commercialize XMT-2056. GSK has not exercised this option to date.

On October 31, 2023 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, reported new nonclinical data at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) on innovations designed to shorten tumor infiltrating lymphocyte (TIL) manufacturing, LYL119, its second generation ROR1-targeted CAR T cell product candidate, as well as data on new technologies and the design of its two clinical trials in progress (Press release, Lyell Immunopharma, OCT 31, 2023, View Source [SID1234636536]).

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"We remain confident that generating T cells with the ability to resist exhaustion and qualities of durable stemness will unlock the potential of effective cell therapy for solid tumors, and our SITC (Free SITC Whitepaper) presentations highlight the progress we are making across our robust pipeline of product candidates and platform technologies designed to achieve this," said Gary Lee, Ph.D., chief scientific officer at Lyell. "We also highlight new data on our Epi-R P2 manufacturing process, a manufacturing innovation designed to enable faster delivery of TIL product to patients without sacrificing the desired yield, stemness phenotype and retention of tumor reactive clones."

Details on the presentations are below.

New Nonclinical Data on LYL119, Innovation in Manufacturing and New Technologies

Four presentations highlight new nonclinical data from Lyell’s product pipeline and research programs, including:

Lyell’s novel Epi-R P2 manufacturing protocol to shorten delivery time of TIL product to patients
New nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell therapy
A new technology being advanced through a collaboration between Lyell and Outpace to enable tumor-restricted IL-12 activity to enhance solid tumor T cell therapies
Lyell’s rejuvenation technology which has shown the potential to "turn back" the epigenetic clock to generate more stem-like T cells with reduced epigenetic age and enhanced proliferation ability
A presentation titled "Epi-R P2 protocol produces a scalable polyclonal TIL product with a greater expansion success rate across hot and cold tumors in shorter culture time" highlights Lyell’s Epi-R P2 manufacturing protocol that shortens manufacturing time for TIL while maintaining the desired yield, stemness phenotype and retention of tumor reactive clones. Current TIL production time is approximately four to six weeks. Literature suggests that a shorter culture time is associated with improved cell quality, functionality and positive clinical outcomes in metastatic melanoma patients. Lyell’s Epi-R manufacturing protocols are designed to generate populations of TIL with stem-like properties to potentially improve antitumor activity. Epi-R P2 is an improved TIL manufacturing process that reduces the TIL culture duration to less than three weeks without impacting the quality of TIL.

Presentation details: Abstract # 379, Friday, Nov. 3, 12–1:30 p.m. and 5:10–6:40 p.m.
New nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell therapy, is highlighted in a presentation titled "Preclinical development of LYL119, a ROR1-targeted CAR T-cell product incorporating four novel T-cell reprogramming technologies to overcome barriers to effective cell therapy for solid tumors." LYL119 incorporates four of Lyell’s complementary, stackable T-cell reprogramming technologies to create potent ROR1-targeted CAR T cells with durable function. In this study, LYL119 demonstrated superior cytotoxicity and sustained cytokine production upon repeated antigen stimulation compared to various controls lacking one or more of the reprogramming technologies and showed robust in vivo antitumor efficacy in a mouse xenograft tumor model at very low cell doses.

Presentation details: Abstract #278, Saturday, Nov. 4, 2023, 11:55–1:25 p.m. and 7–8:30 p.m.
A presentation titled "Protein design and inducible expression allow context-dependent, localized IL-12 activity to enhance solid tumor T cell therapies" highlights an innovative tumor-restricted IL-12 (trIL-12) technology that delivers potent IL-12 stimulation at the tumor site while avoiding systemic exposure. IL-12 is an immune-stimulatory cytokine that can induce potent anti-tumor activity, but systemic delivery of IL-12 has been shown to cause severe toxicity in patients. trIL-12 was designed leveraging Outpace’s OutSmart technology to rapidly auto-inactivate IL-12 after inducible secretion from engineered T cells with the aim of achieving safe, local delivery of IL-12 activity. trIL-12 is being advanced under a collaboration between Lyell and Outpace with the goal of improving efficacy for T-cell therapies while maintaining a favorable safety profile.

Presentation details: Abstract #1047, Friday, Nov. 3, 12–1:30 p.m. and 5:10–6:40 p.m.
A presentation titled "Rejuvenation of tumor-infiltrating lymphocytes (TIL) through Partial Reprogramming" describes Lyell’s rejuvenation technology which has shown the potential to "turn back" the epigenetic clock to generate more stem-like T cells with reduced epigenetic age and enhanced proliferation ability. Previously published studies have demonstrated the decline in T-cell function as a person ages. These new nonclinical data show TIL rejuvenated with Lyell’s technology retain a broad TCR repertoire and demonstrate improved T-cell function and antitumor properties.

Presentation details: Abstract #393, Friday, Nov. 3, 2023, 12–1:30 p.m. and 5:10–6:40 p.m.
Clinical Trials in Progress

Two additional presentations highlight the design of Lyell’s two ongoing Phase 1 clinical trials in progress.

A presentation titled "Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell therapy enhanced with genetic and epigenetic reprogramming, in advanced triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC)" describes the design of this dose-escalation, dose-expansion Phase 1 trial in patients with ROR1-positive relapsed refractory TNBC and NSCLC.

Presentation details: Abstract #754, Saturday, Nov. 4, 2023, 11:55–1:25 p.m. and 7–8:30 p.m.
A presentation titled "Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte (TIL) therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors" describes the design of this dose-escalation, dose-expansion Phase 1 trial in advanced solid tumors, including advanced melanoma, NSCLC and colorectal cancer

Presentation details: Abstract #747, Friday, Nov. 3, 2023, 12–1:30 p.m. and 5:10–6:40 p.m.

On October 31, 2023 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that preliminary topline results from the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) study showed that VAL-083 did not perform better than the current standards of care in glioblastoma (Press release, Kintara Therapeutics, OCT 31, 2023, View Source [SID1234636533]). These topline results included preliminary safety data for VAL-083 that was similar to that of the current standards of care used to treat glioblastoma. With this study outcome, Kintara is suspending the development of VAL-083 and turning its focus to its second program, REM-001. In addition to focusing on its REM-001 program, Kintara will evaluate a wide range of strategic options aimed at potentially maximizing shareholder value.

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"Glioblastoma represents a high unmet medical need, and patients with this disease have very few treatment options," said Robert E. Hoffman, President and Chief Executive Officer of Kintara. "We are very disappointed that the VAL-083 GBM AGILE Study preliminary results do not support continued development efforts to give patients additional treatment options. We sincerely appreciate the exceptional support from patients and their families as well as patient advocates, physicians and our employees who have been committed to the rigorous study of VAL-083. As we shift priorities, we look forward to enrolling our first patient in our 15-patient study of REM-001 in cutaneous metastatic breast cancer (CMBC). Additionally, we will conduct a thorough review of potential strategic opportunities for us to maximize shareholder value in the Company."

"GBM AGILE is a rigorous mechanism for us to efficiently evaluate investigational drugs in a well-controlled, randomized setting," said Meredith Buxton, CEO and President of Global Coalition of Adaptive Research, Sponsor of GBM AGILE. "While we are disappointed that the preliminary results for VAL-083 did not show benefit over standard of care, GBM AGILE is operating as designed and we await final data for VAL-083 in 2024 to better understand if there are possible pathways for further development."

All development activities and related costs for VAL-083 will be suspended while the Company awaits the full dataset from the GBM AGILE Study which is expected at the end of the first quarter/beginning of second quarter of calendar year 2024. At such time Kintara will analyze the full results as it seeks to maximize the value of the VAL-083 asset.

Kintara expects to enroll the first subject in a 15-patient CMBC study around the end of calendar year 2023. The Company was recently awarded a $2 million grant from the National Institutes of Health (NIH) which is expected to cover the majority of the cost to run the CMBC study. In November 2022, the United States Food and Drug Administration (FDA) granted Fast Track Designation (FTD) to Kintara’s REM-001 Therapy for the treatment of patients with CMBC.

REM-001 is a proprietary, late-stage photodynamic therapy platform that holds promise as a localized cutaneous, or visceral, tumor treatment as well as in other potential indications. REM-001 Therapy, which consists of the laser light source, the light delivery device, and the REM-001 drug product, has been previously studied in four Phase 2/3 clinical trials in patients with CMBC who had previously received chemotherapy and/or failed radiation therapy. In CMBC, REM-001 has a clinical efficacy to date of 80% complete responses of CMBC evaluable lesions and an existing robust safety database of approximately 1,100 patients across multiple indications.

On October 31, 2023 Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a biopharmaceutical company with a pipeline of immune-modulating assets designed to target a spectrum of cardiovascular and autoimmune diseases, reported third quarter 2023 financial results and recent portfolio execution (Press release, Kiniksa Pharmaceuticals, OCT 31, 2023, View Source [SID1234636532]).

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"We continue to advance all aspects of our business, including strong revenue growth with ARCALYST and clinical trial execution with KPL-404, and we have cash runway into at least 2027," said Sanj K. Patel, Chairman and Chief Executive Officer of Kiniksa. "On the commercial side, we are building the recurrent pericarditis market and are focused on helping as many patients as possible. We are currently tracking to the high end of our previously issued guidance of $220 million to $230 million in product revenue. Within our clinical development portfolio, we have completed enrollment in the third cohort of the Phase 2 trial of KPL-404 in rheumatoid arthritis. We now expect data from Cohorts 1-3 in the first quarter of 2024."

Portfolio Execution

ARCALYST (IL-1α and IL-1β cytokine trap)

· ARCALYST net product revenue was $64.8 million for the third quarter of 2023.

· Since launch, more than 1,450 prescribers have written ARCALYST prescriptions for recurrent pericarditis.

· As of the end of the third quarter of 2023, average total duration of ARCALYST therapy in recurrent pericarditis was approximately 20 months.

- Average total duration of therapy includes the approximately 45% of patients who restarted ARCALYST, within an average of 8 weeks, after having discontinued therapy.

1

KPL-404 (monoclonal antibody inhibitor of CD40-CD154 interaction)

· Kiniksa completed enrollment of the third cohort of the Phase 2 clinical trial of KPL-404 in rheumatoid arthritis. The company now expects data from Cohorts 1-3 in the first quarter of 2024.

· Kiniksa is currently enrolling a fourth cohort (Cohort 4) of the Phase 2 clinical trial of KPL-404 in rheumatoid arthritis. The additional cohort will evaluate a fixed dose level administered as a single subcutaneous injection once monthly. The company expects data from Cohort 4 in the second quarter of 2024.

Mavrilimumab (monoclonal antibody inhibitor targeting GM-CSFRα)

· Kiniksa is pursuing collaborative study agreements to evaluate the potential of mavrilimumab in rare cardiovascular diseases where the granulocyte macrophage colony stimulating factor (GM-CSF) mechanism has been implicated.

Financial Results

· ARCALYST net product revenue for the third quarter of 2023 was $64.8 million, compared to $33.4 million for the third quarter of 2022.

- Total revenue for the third quarter of 2023 was $67.0 million, including $2.2 million in license and collaboration revenue, compared to total revenue for the third quarter of 2022 of $99.1 million, including $65.7 million in license and collaboration revenue.

· Total operating expenses for the third quarter of 2023 were $78.0 million, compared to $52.7 million for the third quarter of 2022.

- Total operating expenses for the third quarter of 2023 included $17.3 million in collaboration expenses, due to increasing ARCALYST profitability, compared to $4.6 million for the third quarter of 2022.

- Total operating expenses for the third quarter of 2023 included $6.8 million in non-cash, share-based compensation expense, compared to $6.0 million for the third quarter of 2022.

· Net loss for the third quarter of 2023 was $13.9 million, compared to net income of $224.1 million for the third quarter of 2022.

· As of September 30, 2023, Kiniksa had $201.1 million of cash, cash equivalents, and short-term investments and no debt.

Financial Guidance

· Kiniksa expects 2023 ARCALYST net product revenue of between $220 million and $230 million.

· Kiniksa expects that its cash, cash equivalents, and short-term investments will fund its current operating plan into at least 2027.

Conference Call Information

· Kiniksa will host a conference call and webcast at 8:30 a.m. Eastern Time on Tuesday, October 31, 2023, to discuss third quarter 2023 financial results and recent portfolio execution.

· Individuals interested in participating in the call via telephone may register here. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. To access the webcast, please visit the Investors and Media section of Kiniksa’s website. A replay of the event will also be available on Kiniksa’s website within approximately 48 hours after the event.

On October 31, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported the publication of abstracts for poster presentations reporting clinical data and trial design for tumor infiltrating lymphocyte (TIL) therapies at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting in San Diego, CA, November 1-5, 2023 (Press release, Iovance Biotherapeutics, OCT 31, 2023, View Source [SID1234636531]).

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An abstract on the four-year analysis of pooled Cohorts 2 and 4 of the C-144-01 trial reports the longest follow-up data on lifileucel treatment outcomes in the largest population of patients with anti–PD-1–refractory advanced melanoma treated with TIL therapy. As of the data cutoff date of June 16, 2023, median C-144-01 trial follow-up was 48.1 months in heavily pretreated patients with advanced melanoma. One-time lifileucel TIL therapy demonstrated durable efficacy with a four-year OS rate of 22.2%. The longest response was ongoing at 59.9 months. Treatment-emergent adverse events were consistent with known safety profiles of lymphodepletion and IL-2, and their incidence decreased over time. The four-year analysis further supports the use of lifileucel as a potential treatment option in these patients that is differentiated from other immunotherapies.

Iovance Posters at SITC (Free SITC Whitepaper) Annual Meeting

Long-term efficacy and safety of lifileucel tumor infiltrating lymphocyte (TIL) cell therapy in patients with advanced melanoma: A 4-year analysis of the C-144-01 study
Poster: Saturday, Nov. 4, 2023, 9:00 a.m.–8:30 p.m. PT
Tumor infiltrating lymphocytes (TIL) with inducible and membrane-bound IL-12 exhibit superior antitumor activity in vitro
Poster: Friday, Nov. 3, 2023, 9:00 a.m.–7:00 p.m. PT
Trial-in-Progress: TILVANCE-301, a phase 3 study of lifileucel tumor infiltrating lymphocyte (TIL) cell therapy combined with pembrolizumab (pembro) vs pembro alone in treatment-naïve unresectable or metastatic melanoma
Poster: Saturday, Nov. 4, 2023, 9:00 a.m.–8:30 p.m. PT