On August 13, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported financial results and operational highlights for the second quarter ended June 30, 2024 (Press release, Adicet Bio, AUG 13, 2024, View Source [SID1234645836]).

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"We believe ADI-001 has best-in-class potential for autoimmune diseases and we are excited about the opportunity to expand ADI-001 clinical development beyond LN to include patients with SLE, SSc and AAV. We have initiated startup activities at multiple clinical sites and expect to begin enrolling patients with LN in our Phase 1 study in the third quarter of 2024," said Chen Schor, President and Chief Executive Officer at Adicet Bio. "Looking ahead, with the ADI-270 IND cleared for RCC, and Fast Track Designation in hand, we expect to initiate the Phase 1 trial of ADI-270 in patients with RCC, the most common type of kidney cancer, in the fourth quarter of 2024. This progress underscores the unique potential of our gamma delta 1 CAR T cell platform in both autoimmune diseases and solid tumors."

Second Quarter 2024 and Recent Operational Highlights:

Autoimmune diseases

Fast Track Designation for ADI-001 in relapsed/refractory class III or class IV LN. In June 2024, the FDA granted ADI-001 Fast Track Designation for the potential treatment of relapsed/refractory class III or class IV LN. The Company has initiated startup activities at multiple clinical sites and plans to commence enrollment in its Phase 1 clinical trial of ADI-001 in lupus nephritis in the third quarter of 2024, with preliminary clinical data expected in the first half of 2025, subject to site initiation and patient enrollment.
Expansion of clinical development of ADI-001 beyond LN to include SLE, SSc and AAV. The Company recently received clearance for its IND to include three additional indications: SLE, SSc and AAV. In connection with the Company’s Phase 1 clinical trial of ADI-001 in autoimmune disease, enrollment of SLE, SSc and AAV patients is expected to commence in the second half of 2024. Clinical data from the Company’s Phase 1 clinical trial of ADI-001 in SLE, SSc and AAV patients are anticipated during the first half of 2025, subject to site initiation and patient enrollment expectations.
Hematologic malignancies and solid tumor indications

IND clearance and FDA Fast Track Designation for ADI-270. Adicet received FDA clearance of its IND application for ADI-270 in RCC and the FDA also granted Fast Track Designation for ADI-270 for the potential treatment of patients with metastatic/advanced clear cell RCC who have been treated with an immune checkpoint inhibitor and a vascular endothelial growth factor inhibitor. Contingent upon study initiation progress, the Company intends to initiate the Phase 1 clinical trial of ADI-270 in RCC patients in the fourth quarter of 2024 and present preliminary clinical data from the study in the first half of 2025, subject to site initiation and patient enrollment.
Presentation of preclinical data from ADI-270 at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress. In June 2024, Adicet presented promising preclinical data supporting ADI-270’s robust anti-tumor activity in an encore poster presentation at the EHA (Free EHA Whitepaper) Hybrid Congress.
Enrollment of mantle cell lymphoma (MCL) patients ongoing in ADI-001 Phase 1 GLEAN study. Adicet is continuing to enroll MCL patients in the Phase 1 trial evaluating ADI-001 in relapsed or refractory non-Hodgkin’s Lymphoma. The Company plans to provide a clinical update in the fourth quarter of 2024.
Financial Results for Second Quarter 2024:

Research and Development (R&D) Expenses: R&D expenses were $25.9 million for the three months ended June 30, 2024, compared to $28.4 million during the same period in 2023. The decrease in research and development expenses was primarily due to a net $1.9 million decrease in expenses related to contract development and manufacturing organization and other externally conducted research and development as well as a $0.6 million decrease in payroll and personnel expenses resulting from a decrease in overall headcount.
General and Administrative (G&A) Expenses: G&A expenses were $6.9 million for the three months ended June 30, 2024, compared to $6.5 million during the same period in 2023. The increase in general and administrative expenses was primarily due to an increase in stock-based compensation of $0.7 million. The increase was partially offset by a $0.2 million decrease in recruiting fees as well as a $0.1 million decrease in consultant fees.
Net Loss: Net loss for the three months ended June 30, 2024 was $29.9 million, or a net loss of $0.33 per basic and diluted share, including non-cash stock-based compensation expense of $6.0 million, as compared to a net loss of $32.4 million, or a net loss of $0.75 per basic and diluted share, including non-cash stock-based compensation expense of $5.0 million during the same period in 2023.
Cash Position: Cash and cash equivalents were $224.1 million as of June 30, 2024, compared to $159.7 million as of December 31, 2023. The Company expects that current cash and cash equivalents as of June 30, 2024, will be sufficient to fund its operating expenses into the second half of 2026.

On August 13, 2024 CSL reported its results presentation for the full year ended 30 June 2024 (Presentation, CSL, AUG 13, 2024, View Source [SID1234647101]).

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On August 13, 2024 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune diseases, reported business highlights and financial results for the second quarter ended June 30, 2024 (Press release, Fate Therapeutics, AUG 13, 2024, View Source [SID1234645804]).

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"We are pleased with the initial clinical and translational observations from our three ongoing Phase 1 studies and look forward to sharing data from each program in the second half of 2024," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We remain keenly focused on achieving therapeutic differentiation in autoimmunity with our off-the-shelf FT819 CAR T-cell and FT522 CAR NK cell product candidates. Our ongoing FT819 study for systemic lupus erythematosus now includes single-agent cyclophosphamide as an alternative conditioning regimen for patients, and we are working to expand clinical investigation of FT819 to treat additional B cell-mediated diseases. We are also finalizing our FT522 IND submission for the treatment of a basket of autoimmune diseases without administration of conditioning chemotherapy to patients, having now treated the first patient without conditioning chemotherapy in our ongoing FT522 study for B cell lymphoma. In addition, under our solid tumor collaboration with Ono Pharmaceutical, we have now treated the first three patients as monotherapy with our multiplexed-engineered FT825 CAR T-cell collaboration candidate, and we are poised to initiate dosing in combination with monoclonal antibody therapy to explore the potential of dual-antigen targeting in advanced solid tumors."

FT819 iPSC-derived 1XX CAR T-cell Program

Enrollment Ongoing in FT819 Phase 1 Autoimmunity Study. The multi-center, Phase 1 clinical trial for patients with systemic lupus erythematosus (SLE) is designed to evaluate the safety, pharmacokinetics, and anti-B cell activity of FT819, the Company’s off-the-shelf CD8αβ+ T-cell product candidate that incorporates a CD19-targeted chimeric antigen receptor (CAR) with a novel 1XX costimulatory domain into the T-cell receptor alpha constant (TRAC) locus (NCT06308978). The first patient treated in the study, a 27 year-old woman diagnosed with lupus nephritis over ten years ago who has refractory disease despite having been treated with multiple standard-of-care therapies, received conditioning chemotherapy followed by a single dose of FT819 at 360 million cells. The patient remains on-study, and there have been no Grade ≥3 adverse events and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). The Company plans to present clinical and translational data from the Phase 1 study at a medical conference in the second half of 2024.
Single-agent Cyclophosphamide Included as Alternative Conditioning Regimen. In addition to conditioning of patients with either cyclophosphamide and fludarabine (Cy / Flu) or bendamustine, the Company amended the clinical protocol of its FT819 Phase 1 autoimmunity study to include single-agent cyclophosphamide (Cy) as a third conditioning regimen. Cy is a commonly-used agent with an established safety profile for the treatment of patients with B cell-mediated autoimmune diseases.
Favorable Safety Profile and Proof-of-Concept for Autoimmune Disease Established in FT819 Phase 1 BCM Study. At the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 27th Annual Meeting in May, the Company presented clinical and translational data from its FT819 Phase 1 study in relapsed / refractory B cell malignancies (BCM) (NCT04629729). 43 heavily pre-treated patients were treated with conditioning chemotherapy and a single dose of FT819 across five dose levels. The safety and tolerability profile of FT819 was favorable, with no dose-limiting toxicities, no events of any grade of ICANS or GvHD, and low incidence (14%) of low-grade CRS. In addition, a single dose of FT819 exhibited multiple mechanisms implicated in generating an immune reset in patients with B cell-mediated autoimmune diseases, including rapid, deep, and sustained CD19+ B-cell depletion in the periphery throughout the one-month treatment cycle as well as primary, secondary, and tertiary tissue trafficking, infiltration, and activity with CD19+ B cell elimination in tissue. The Company successfully completed dose escalation in its FT819 Phase 1 BCM study, and has focused further clinical development of FT819 exclusively in autoimmunity.
FT825 / ONO-8250 iPSC-derived CAR T-cell Program

Enrollment Ongoing in Phase 1 Study with HER2-targeted CAR T-cell for Advanced Solid Tumors. Under its collaboration with Ono Pharmaceutical Co., Ltd. (Ono), the Company is conducting a multi-center, Phase 1 study to assess the safety, pharmacokinetics, and activity of FT825 / ONO-8250 as monotherapy and in combination with monoclonal antibody therapy in patients with advanced solid tumors (NCT06241456). Designed using the Company’s iPSC product platform, FT825 / ONO-8250 incorporates seven synthetic controls of cell function including a novel cancer-specific H2CasMab-2 CAR, which has exhibited similar potency with greater specificity for cancer cells expressing HER2 compared to trastuzumab in preclinical studies. Three patients have been treated in the Phase 1 study with a single dose of FT825 / ONO-8250 as monotherapy at the first dose level of 100 million cells and, during the third quarter of 2024, the Company plans to initiate enrollment as monotherapy at the second dose level of 300 million cells and in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy at the first dose level of 100 million cells. The Company plans to present clinical and translational data from the Phase 1 study at a medical conference in the second half of 2024.
FT522 iPSC-derived CAR NK Cell Program

First Patient Treated without Conditioning in Phase 1 BCL Study. FT522 is the Company’s off-the-shelf, CD19-targeted CAR NK cell product candidate and its first to incorporate Alloimmune Defense Receptor (ADR) technology, which is designed to reduce or eliminate the need for administration of conditioning chemotherapy to patients receiving cell therapies. In its ongoing multi-center, Phase 1 clinical trial of FT522 in patients with relapsed / refractory B-cell lymphoma (BCL) (NCT05950334), the first patient has now been treated in the first three-dose cohort at 300 million cells per dose without conditioning chemotherapy (Regimen B). In addition, the first patient has now been treated in the second three-dose cohort at 900 million cells per dose with conditioning chemotherapy (Regimen A). No dose-limiting toxicities and no events of any grade of CRS, ICANS, or GvHD, have been reported in the Phase 1 study. The Company plans to present clinical and translational data from the Phase 1 study at a medical conference in the second half of 2024.
IND Application for Phase 1 Basket Study in Autoimmunity to be Submitted in 3Q24. The Company intends to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in the third quarter of 2024 for the treatment of a basket of B cell-mediated autoimmune diseases with FT522, including without administration of conditioning chemotherapy to patients. At the ASGCT (Free ASGCT Whitepaper) conference, the Company presented preclinical data from a novel re-challenge assay using peripheral blood mononuclear cells (PBMCs) from unmatched SLE donors, showing that FT522 uniquely drove rapid and deep CD19+ B cell depletion, eliminated alloreactive T cells, and maintained functional persistence, indicating that FT522 can function effectively in the presence of an unmatched host immune system. The Company also shared initial clinical observations from the first two patients treated with FT522 at 100 million cells per dose in Regimen A of its ongoing Phase 1 BCL study, which showed rapid, deep, and sustained B-cell depletion in the periphery throughout the one-month treatment cycle. In addition, both patients showed enhanced persistence of FT522 in the periphery compared to clinical data observed with FT596, a prior-generation CD19-targeted CAR NK cell without ADR technology.
Second Quarter 2024 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of June 30, 2024 were $352.0 million.
Total Revenue: Revenue was $6.8 million for the second quarter of 2024, which was derived from the achievement of a $5 million milestone in connection with the clinical development of FT825 / ONO-8250 and the conduct of preclinical development activities for a second collaboration candidate targeting an undisclosed solid tumor antigen under its collaboration with Ono.
Total Operating Expenses: For the second quarter of 2024, GAAP operating expenses were $51.9 million, including research and development expenses of $34.6 million and general and administrative expenses of $17.3 million. Such amounts included $9.6 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 113.8 million, pre-funded warrants outstanding were 3.9 million, and preferred shares outstanding were 2.8 million, as of June 30, 2024. Each preferred share is convertible into five common shares.

On August 13, 2024 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel class of oncolytic immunotherapies, reported that the first patient has been randomized and dosed in the IGNYTE-3 study – a global Phase 3 clinical trial assessing the efficacy and safety of RP1 (vusolimogene oderparepvec) plus nivolumab in patients with advanced melanoma who have progressed on anti-PD1 and anti-CTLA-4 drugs or are ineligible for anti-CTLA-4 treatment (Press release, Replimune, AUG 13, 2024, View Source [SID1234645821]).

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"The start of the IGNYTE-3 trial and randomization of the first patient is an important milestone in advance of our planned BLA submission of RP1 in advanced melanoma later this year," said Kostas Xynos, MD, PhD, MBA, Chief Medical Officer at Replimune. "This trial is important because it is intended to both support global regulatory interactions and access, and to serve to confirm the clinical benefit reported from the registration intended Phase 2 IGNYTE cohort in anti-PD1 failed melanoma in June."

Melanoma is the fifth most common cancer with approximately 100,000 new cases and 8,000 deaths estimated in the U.S. in 2024. Standard of care therapy includes treatment with immune checkpoint blockade, to which approximately half of patients will not respond or will progress following treatment. Treatment options are limited after immune checkpoint blockade therapy, with no standard of care available to patients.

"Clinical trials like IGNYTE-3 are important in the melanoma community and we are excited that another study is open for physicians and patients to consider," said Kyleigh LiPira, CEO of the Melanoma Research Foundation. "As a patient advocacy organization, our mission is to eradicate melanoma by accelerating medical research while educating to and advocating for the melanoma community. Creating awareness for clinical trials is an important part of that mission."

The IGNYTE-3 trial (NCT06264180) will enroll 400 patients and evaluate RP1 plus nivolumab versus a defined list of physician’s choice treatment options, in patients with advanced melanoma who progressed on anti-PD1 and anti-CTLA-4 therapy or who are ineligible for anti-CTLA-4 treatment. The primary endpoint of the study is overall survival (OS). Key secondary endpoints are progression free survival (PFS) and objective response rate (ORR). For additional information about the IGNYTE-3 trial and to learn more about eligibility, please visit View Source

About RP1
RP1 (vusolimogene oderparepvec) is Replimune’s lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF, intended to maximize tumor killing potency, the immunogenicity of tumor cell death, and the activation of a systemic anti-tumor immune response.

On August 13, 2024 NorthStar Medical Radioisotopes, LLC, a global innovator in the development, production, and commercialization of radiopharmaceuticals used for therapeutic applications and medical imaging, and Convergent Therapeutics, Inc., a clinical stage radiopharmaceutical company, reported the signing of a strategic contract manufacturing services agreement (Press release, NorthStar Medical Radiostopes, AUG 13, 2024, View Source [SID1234645837]). Convergent’s lead asset CONV01-α is a prostate-specific membrane antigen (PSMA)-targeted monoclonal antibody linked to Ac-225 and is currently being investigated as a treatment for prostate cancer.

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Under the terms of the expanded collaboration, NorthStar will:

Provide Convergent with its environmentally preferred, high purity non-carrier-added (n.c.a) Ac-225 for use in CONV01-α,
Utilize its new, state-of-the-art contract development and manufacturing facility to manufacture CONV01-α to serve patients in Convergent’s clinical trials, and
Perform research and development activities to support continued development of CONV01-α and other Convergent assets.
In March of this year, Convergent received U.S. Food and Drug Administration ("FDA") clearance for its investigational new drug ("IND") application for CONV01-α, a key milestone that enables Convergent to advance CONV01-α into Phase 2 studies and expand the scope of clinical development of CONV01-α as a monotherapy and in combination with other cancer therapies. The manufacturing supply agreement announced today will support these trials and, if U.S. FDA approved, the manufacturing of CONV01-α for commercial purposes.

"The last several years have seen an explosion of research and clinical trials in the area of radiotherapies, especially those using Ac-225," said Frank Scholz, Chief Executive Officer of NorthStar, "and yet today there are still far too few effective therapies for patients suffering from a variety of serious diseases including many cancers. Why? Because the processes to develop, manufacture and deliver therapeutically effective radiopharmaceuticals like Convergent’s CONV01-α to market – in particular at a scale able to meet patient demand for an approved, marketed medicine — are highly specialized and complex. At NorthStar, our passion is to reduce technological and operational barriers to help companies like Convergent Therapeutics not only secure a reliable source of Ac-225, but manufacture a finished, patient-ready drug product and continue to develop new and additional therapeutic indications for the patients who need new and better medicines. We are proud to be supporting Convergent and look forward to working with them to help make new medicines like CONV01-α therapeutic reality."

"We are excited to expand our partnership with NorthStar and the opportunity to leverage NorthStar’s unique position to scale both Ac-225 generation and manufacturing capacity," said Caitlyn Harvey, Head of Manufacturing at Convergent. "Convergent will begin enrolling patients into the CONVERGE-01 Phase 2 clinical trial in the next couple of months as we continue building on extensive clinical experience which will allow us to rapidly move into our Phase 3 study."

About CONV01-α

CONV01-α, Convergent’s alpha emitting radioantibody, combines the precision and pharmacokinetics of antibodies with the tumor-killing potential of alpha emitting radionuclides. Specifically, CONV01-α uses a humanized monoclonal antibody targeted at prostate-specific membrane antigen (PSMA) which is highly overexpressed in prostate cancer cells. Since PSMA is a validated target, several therapeutics are directed at this antigen and CONV01-α is differentiated by its use of both an antibody and alpha emitter. CONV01-α is linked to a powerful radionuclide called Ac-225, which releases alpha particles which kill cancer cells through DNA double strand breaks. Unlike other radioactive sources, alpha particles deliver high-energy radiation over very short distances, thereby minimizing radiation exposure to healthy neighboring cells and tissues. Pairing highly selective antibodies with such a powerful yet precise payload offers the ideal combination to treat many types of cancers.