On December 13, 2022 Galapagos NV (Euronext & NASDAQ: GLPG) and CellPoint (a Galapagos company) reported encouraging initial data from the ongoing ATALANTA-1 Phase 1/2 study with GLPG5101 at the 64th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Congress taking place in New Orleans, Louisiana, from 10-13 December (Press release, Galapagos, DEC 13, 2022, View Source [SID1234625207]).

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ATALANTA-1 is a Phase 1/2 study in heavily pre-treated rrNHL patients to evaluate the safety, efficacy, and feasibility of GLPG5101, a fresh CD19 CAR-T product candidate manufactured at point-of-care. The dose levels that are evaluated in the Phase 1 part of the study are 50×106 (DL1), 110×106 (DL2) and 250×106 (DL3). As of 8 November 2022, 9 patients were enrolled; baseline and safety data for 8 patients were available (n=4 at DL1; n=4 at DL2). 7 patients reached the follow-up period of 28-days and were eligible for efficacy evaluation.

The initial results from 7 patients that were eligible for efficacy evaluation (cut-off date: 8 November 2022) indicated that a 7-day vein-to-vein time is feasible and demonstrated strong and consistent in vivo CAR-T expansion levels. Moreover, the initial efficacy results are encouraging with an objective response rate (ORR) of 86% observed and all responding patients achieving a complete response (CR). A duration of response of up to 7 months has been reported and follow-up is ongoing. Two patients who received DL1 that progressed after initial stable disease or CR respectively, had a CD19-negative escape. No CD19-positive relapses have been observed.

In the safety analysis of these 7 patients, adverse events were consistent with the known toxicities of CD19 CAR-T treatment. No grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in any of the patients. At DL2, CRS grade 1 or 2 was reported in 4 patients and ICANS grade 1 was reported in 3 patients. Patients at DL1 did not experience any grade of CRS or ICANS. Dose-limiting toxicity (neutropenia grade 4 for >21 days) was observed in 1 patient (DL2) and the majority of grade ≥3 adverse events were hematological toxicities.

"We are committed to accelerating transformational innovation to address unmet needs of patients with advanced cancers," said Dr. Paul Stoffels1, CEO and Chairman of the Board of Directors of Galapagos. "Despite significant medical advancements in recent years, many cancer patients relapse, become resistant to treatment or are diagnosed too late. We believe that differentiation and broader access to therapy can come from a disruptive CAR-T manufacturing model at the point-of-care, closer to patients. We are excited to present initial encouraging safety, efficacy and feasibility data from the ATALANTA-1 study with GLPG5101 manufactured at point-of-care, which support that potential. We are on track to report topline data from the completed study in the first half of 2023."

The poster presentation was given by Marie José Kersten, MD, PhD, Professor of Hematology and Head of the Department of Hematology at the Academic Center in Amsterdam:

Abstract Title Authors Presentation date/time
Initial Clinical Results of ATALANTA-1, a Phase 1/2 Trial of Point-of-Care Manufactured GLPG5101 (19CP02) in rrNHL Sébastien Anguille, Ilse Kuipers, Kirsten Saevels, Yves Beguin, Anna Van Muyden, Christian Jacques, and Marie José Kersten Poster Number: 4637
Date: 12 December 2022, 6:00–8:00 PM ET
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III
CellPoint has developed, in a strategic collaboration with Lonza, a novel point-of-care supply model, which is designed to enable clinicians to administer fresh CAR T cells within 7 days of leukapheresis, without complex logistics or cryopreservation, thereby aiming to address important limitations of current CAR-T treatments. The proprietary platform consists of CellPoint’s end-to-end xCellit workflow management and monitoring software and Lonza’s Cocoon Platform, a functionally closed, automated manufacturing platform for cell therapies.

About the ATALANTA-1 study (EudraCT 2021-003272-13)
ATALANTA-1 is an ongoing Phase 1/2, open-label, multicenter study to evaluate the feasibility, safety, and efficacy of point-of-care manufactured GLPG5101, a CD19 CAR-T product candidate, in patients with relapsed/refractory Non-Hodgkin Lymphoma (rrNHL). GLPG5101 is a second generation anti-CD19/4-1BB CAR-T product candidate, administered as an intravenous infusion of a fresh product candidate in a single fixed dose. Each enrolled patient will be followed for 24 months. The primary objective of the Phase 1 part of the study is to evaluate safety and to determine the recommended dose for the Phase 2 part of the study. Secondary objectives include assessment of efficacy and feasibility of point-of-care manufacturing of GLPG5101. The planned dose levels that are evaluated in the Phase 1 are 50×106, 110×106 and 250×106 CAR T cells. The primary objective of the Phase 2 part of the study is to evaluate the objective response rate (ORR) while the secondary objectives include complete response rate (CRR), duration of response, progression free survival, overall survival, safety, pharmacokinetic profile, and feasibility of point-of-care manufacturing. The study is currently enrolling rrNHL patients in Europe and the first expansion cohort for Mantle Cell Lymphoma, a form of NHL, is currently open for recruitment. The company aims to broaden the study to include US patients in 2023 and to provide topline results in the first half of 2023.

About Non-Hodgkin’s Lymphoma
Non-Hodgkin’s lymphoma is a cancer originating from lymphocytes, a type of white blood cell which is part of the body’s immune system. Non-Hodgkin’s lymphoma can occur at any age although it is more common in adults over 50 years old. Initial symptoms usually are enlarged lymph nodes, fever, and weight loss. There are many different types of Non-Hodgkin’s lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow-growing) types, and they can be formed from either B lymphocytes (B cells) or in lesser extent from T lymphocytes (T cells) or Natural Killer cells (NK cells). B-cell lymphoma makes up about 85 percent of Non-Hodgkin’s lymphomas diagnosed in the US. Prognosis and treatment of Non-Hodgkin’s lymphomas depend on the stage and type of disease.

On December 13, 2022 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported preclinical data of several novel strategies designed to enable administration of off-the-shelf cell-based cancer immunotherapies without conditioning chemotherapy at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. Conditioning chemotherapy, commonly used throughout the field of cell therapy, often results in hematologic toxicities, can limit the potential for administration of multiple doses, and can prohibit adoption as part of early-line treatment (Press release, Fate Therapeutics, DEC 13, 2022, View Source [SID1234625206]). Novel strategies to reduce or eliminate the need for conditioning chemotherapy presented by the Company at ASH (Free ASH Whitepaper) include arming iPSC-derived effector cells with an alloimmune defense receptor, which selectively targets and eliminates 41BB-expressing alloreactive host immune cells to promote expansion, persistence, and anti-tumor activity; the genetic ablation of CD38 in combination with CD38-targeted monoclonal antibody therapy, which uniquely targets and depletes CD38-expressing activated host immune cells; and the combined genetic ablation of the adhesion molecules CD54 and CD58, which reduces immune synapse formation resulting in host immune cell evasion.

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"Eliminating the need for conditioning chemotherapy has the potential to significantly improve the safety and clinical benefit of cell therapies, and enable their use in a significantly broader population of patients with hematologic malignancies and solid tumors. Our next-generation iPSC product platform seeks to create the ideal off-the-shelf cell therapy, which would enhance functional persistence and anti-tumor activity while reducing or eliminating the need for conditioning chemotherapy to deplete host lymphocytes," said Bob Valamehr, Ph.D., Chief Research and Development Officer of Fate Therapeutics. "We are developing multiple promising strategies that can only be realized through precise multiplexed-engineering of cells, and we believe our leading iPSC product platform is uniquely positioned to generate clonal NK and T-cell product candidates that can thrive and resist rejection."

Alloimmune Defense Receptor Targeting 4-1BB

The cell surface receptor 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is upregulated on activated CD4+, CD8+, and regulatory T cells as well as activated NK cells of the host immune system. Scientists from the Company and the laboratory of Maksim Mamonkin, Ph.D., Assistant Professor, Cell and Gene Therapy, Baylor College of Medicine, integrated a novel alloimmune defense receptor (ADR) that selectively targets 4-1BB into a master induced pluripotent stem cell (iPSC) line incorporating a CD19-targeted chimeric antigen receptor (CAR), that was subsequently differentiated into NK cells (ADR-armed, CD19-targeted CAR iNK cells). In the ASH (Free ASH Whitepaper) presentation (Abstract #1986), the scientists showed that in an in vitro co-culture assay with allogeneic peripheral blood mononuclear cells (allo PBMCs), ADR-armed, CD19-targeted CAR iNK cells expanded, persisted, and selectively eliminated 4-1BB+ allo PBMCs in contrast to ADR-null CD19-targeted CAR iNK cells, which were depleted. Further, a disseminated Nalm6 leukemia model comprised of allo-reactive T cells and tumor cells resistant to T-cell killing (MHC class 1-null), demonstrated that ADR-armed, CD19-targeted CAR iNK cells exhibited uncompromised effector function in vivo compared to ADR-null CD19-targeted CAR iNK cells, suggesting that ADR-armed NK cells functionally persist, proliferate, and durably kill tumor cells while resisting rejection by allo-reactive T cells.

CD38 Genetic Ablation in Combination with CD38-targeted Monoclonal Antibody Therapy

CD38-targeted monoclonal antibody therapies, such as daratumumab, are approved by the U.S. Food and Drug Administration for the treatment of multiple myeloma. CD38 has also been shown to be highly expressed on activated immune cells, including CD8+ T cells, CD4+ T cells, and NK cells. The Company has incorporated the knock-out of CD38 into its proprietary iPSC product platform, which uniquely allows for CD38-null, iPSC-derived NK cells (CD38-null iNK cells) to be combined with CD38-targeted monoclonal antibody therapies and avoid fratricide. In the ASH (Free ASH Whitepaper) presentation (Abstract #3288), scientists from the Company showed that, in a humanized mouse model containing allogeneic CD38+ activated NK and T cells, administration of daratumumab selectively depleted allogeneic CD38+ NK and T cells and uniquely enabled CD38-null iNK cells to functionally persist through Day 28 compared to wild-type iNK cells. These preclinical data were supported by translational findings from the Company’s Phase 1 study of FT576 (NCT05182073), its multiplexed-engineered, BCMA-targeted CAR NK cell product candidate that incorporates the knock-out of CD38, where combination with daratumumab rapidly and selectively eliminated CD38+ patient immune cells through the first month of therapy. The translational findings suggest that following administration of daratumumab, CD38-null iNK cells may avoid rejection by activated host immune cells without requiring conditioning chemotherapy.

Combined CD54 and CD58 Genetic Ablation

Avoiding NK cell-mediated rejection has been an area of significant research in the field of allogeneic cell therapy. While it has been shown that the knock-out of MHC class-I and MHC class-II molecules can avoid T cell-mediated rejection, engineered cells integrating MHC class-I knock-out are aggressively targeted and eliminated by NK cells. In the ASH (Free ASH Whitepaper) presentation (Abstract #481), scientists from the Company, the laboratory of Karl-Johan Malmberg, M.D., Ph.D., Professor of Immunology, University of Oslo, Norway, and the laboratory of Michel S. Sadelain, M.D., Ph.D., Stephen and Barbara Friedman Chair; Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center presented a novel engineering strategy comprised of the knock-out of four genes: MHC class-I and MHC class-II as well as the adhesion molecules, CD54 and CD58. The scientists showed that the knock-out of CD54 and CD58 confers resistance to NK cell-mediated rejection across the spectrum of NK cell subpopulations compared to other engineering approaches such as HLA-E over-expression, which avoids recognition by NKG2A+ NK cells but induces killing by the most potent sub-set, NKG2C+ NK cells. Using multiplexed-engineered, iPSC-derived NK cells incorporating MHC class-I and MHC class-II knockouts, the scientists showed that the addition of CD54 and CD58 knockouts extended persistence in vivo in a humanized mouse model comprised of allogeneic NK cells.

About Fate Therapeutics’ iPSC Product Platform

The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that are designed to be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

On December 13, 2022 Eli Lilly and Company (NYSE: LLY) reported its 2023 financial guidance, highlighted by expected volume-based revenue growth and increased investments to maximize future value (Press release, Eli Lilly, DEC 13, 2022, View Source [SID1234625198]). The company will review potential key events for the upcoming year, including important data readouts for several investigational medicines in its clinical pipeline and the possibility of multiple regulatory submissions and approvals, in a call with investors today.

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"Lilly is exiting 2022 with momentum. Our approved and available medicines are early in their life cycles and showed accelerated growth during the year, led by a strong Mounjaro launch. In addition, several of our late-stage medicines for serious diseases were submitted for approval this year, and will hopefully launch in 2023," said David A. Ricks, Lilly’s chair and CEO. "We continue to innovate and are beginning new pivotal studies for the next group of potential breakthrough treatments. In the decade ahead, we are well-positioned to create significant value for patients with challenging conditions, health systems struggling to manage chronic disease, and of course, our shareholders."

Anat Ashkenazi, Lilly’s executive vice president and chief financial officer, outlined the company’s expectations for its growth prospects: "We believe we have the potential to deliver top-tier, volume-driven revenue growth through at least 2030 with groundbreaking medicines. In addition to the tremendous on-going launch of Mounjaro in type 2 diabetes and expected future opportunities to treat obesity and obesity-related metabolic outcomes with tirzepatide, we plan to invest in our four significant potential new launches next year. With limited patent expirations this decade, we believe these potential new medicines and the continued scaling of our key growth products will fuel our next wave of growth. Lilly is committed to maximizing long-term value for stakeholders and we look forward to delivering further in 2023."

2022 Financial Guidance

The company reaffirmed its 2022 financial guidance on both a reported and non-GAAP basis. The company’s 2022 financial guidance reflects adjustments shown in the reconciliation table below.

2022

Expectations

% Change vs
2021

Earnings per share (reported)

$6.50 to $6.65

6% to 9%

Net losses on investments in equity securities(1)

.52

Amortization of intangible assets

.51

Asset impairment, restructuring, and other special charges

.17

Earnings per share (non-GAAP)

$7.70 to $7.85

4% to 6%

Numbers may not add due to rounding

Acquired IPR&D and development milestone charges(2)

$.67

(1) The company’s guidance does not reflect the impact of net gains or losses on
investments in equity securities during Q4 2022.

(2) The company’s guidance does not include any acquired IPR&D or development
milestone charges incurred during Q4 2022.

The company reaffirmed its 2022 financial guidance, as set forth in the following table:

2022 Guidance

Revenue

$28.5 to $29.0 billion

Gross Margin % of Revenue (reported)

Approx. 76%

Gross Margin % of Revenue (non-GAAP)

Approx. 78%

Marketing, Selling & Administrative

$6.4 to $6.6 billion

Research & Development

$7.1 to $7.3 billion

Acquired IPR&D & Development Milestones

Approx. $670 million

Other Income/(Expense) (reported)

$(700) to $(600) million

Other Income/(Expense) (non-GAAP)

$(100) million to $0

Tax Rate

Approx. 13% to 14%

Earnings per Share (reported)

$6.50 to $6.65

Earnings per Share (non-GAAP)

$7.70 to $7.85

Operating Margin % (reported)

Approx. 26%

Operating Margin % (non-GAAP)

Approx. 29%

Non-GAAP guidance reflects adjustments presented in the earnings per share table above.

2023 Financial Guidance

Earnings per share (EPS) for 2023 is expected to be in the range of $7.65 to $7.85 on a reported basis and $8.10 to $8.30 on a non-GAAP basis. The company’s 2023 financial guidance reflects the adjustment shown in the reconciliation table below.

2023

Expectations

Earnings per share (reported)

$7.65 to $7.85

Amortization of intangible assets

.45

Earnings per share (non-GAAP)

$8.10 to $8.30

Numbers may not add due to rounding.

The company’s 2023 financial guidance does not include any impact from potential
or pending business development transactions or potential development milestone
charges.

The company anticipates 2023 revenue between $30.3 billion and $30.8 billion, driven by volume increases from key growth products. This growth is expected to be partially offset by lower revenue for Alimta due to its loss of patent exclusivity, no anticipated COVID-19 antibody revenue, and the continued negative impact of foreign exchange rates.

Gross margin as a percent of revenue for 2023 is expected to be approximately 77% on a reported basis and approximately 79% on a non-GAAP basis.

Marketing, selling and administrative expenses for 2023 are expected to be in the range of $6.9 billion to $7.1 billion. Research and development expenses are expected to be in the range of $8.2 billion to $8.4 billion.

Consistent with 2022, the company is not including any potential or pending acquired in-process research and development (IPR&D) and development milestone charges in its initial 2023 guidance and expects to update EPS guidance each quarter as acquired IPR&D and development milestone charges are incurred.

Other income (expense) is expected to be expense in the range of $100 million to $200 million on both a reported and non-GAAP basis.

The 2023 effective tax rate is expected to be approximately 16% on both a reported basis and non-GAAP basis. This assumes the provision in the 2017 Tax Act that requires capitalization and amortization of research and development expenses for tax purposes is deferred or repealed by U.S. Congress this year, effective for the full year 2022 as well as 2023. The tax rate increase also includes the impact from recently enacted Puerto Rico legislation that will become effective starting in 2023, as well as the impact from an expected increase in the proportion of earnings in higher tax jurisdictions.

The following table summarizes the company’s 2023 financial guidance:

2023 Guidance

Revenue

$30.3 to $30.8 billion

Gross Margin % of Revenue (reported)

Approx. 77%

Gross Margin % of Revenue (non-GAAP)

Approx. 79%

Marketing, Selling & Administrative

$6.9 to $7.1 billion

Research & Development

$8.2 to $8.4 billion

Other Income/(Expense)

$(200) million to $(100) million

Tax Rate

Approx. 16%

Earnings per Share (reported)

$7.65 to $7.85

Earnings per Share (non-GAAP)

$8.10 to $8.30

Non-GAAP guidance reflects adjustments presented in the earnings per share table above.

Webcast of Conference Call

As previously announced, investors and the general public can access a live webcast of the 2023 financial guidance conference call through a link on Lilly’s website at investor.lilly.com/webcasts-and-presentations. The conference call will begin at 9 a.m. Eastern time today and will be available for replay via the website.

Non-GAAP Financial Measures

The company uses non-GAAP financial measures that differ from financial statements reported in conformity with U.S. generally accepted accounting principles ("GAAP"), and this press release and related materials includes a description of certain non-GAAP items that may affect the company’s financial expectations for 2022 and 2023. The company’s non-GAAP financial measures adjust reported results to exclude amortization of intangibles and items that are typically highly variable, difficult to predict, and/or of a size that could have a substantial impact on the company’s reported operations for a period. The company believes that these non-GAAP financial measures provide useful information to investors in evaluating the company’s performance. They can assist in making meaningful period-over-period comparisons and in identifying operating trends that would otherwise be masked or distorted by the items subject to the adjustments. Management uses these non-GAAP financial measures internally to evaluate the performance of the company’s business, including to allocate resources and to evaluate results relative to incentive compensation targets. Investors should consider these non-GAAP financial measures in addition to, not as a substitute for or superior to, measures of financial performance prepared in accordance with GAAP.

On December 13, 2022 Lantern Pharma Inc., a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning ("M.L.") platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that it has expanded development of its drug candidate LP-184 to include Triple Negative Breast Cancer (TNBC), one of the most aggressive and malignant forms of breast cancer (Press release, Lantern Pharma, DEC 13, 2022, View Source [SID1234625197]). New positive preclinical data on the anti-tumor potency of LP-184 for TNBCs was recently presented at the San Antonio Breast Cancer Symposium (SABCS) 2022.

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"As many as 20% of all breast cancers are TNBCs, which are tumors that do not express receptors for Estrogen, Progesterone, or HER2. Therefore, drugs targeted at these receptors are not a therapeutic option for TNBC patients. The prognosis of TNBC patients is considerably worse than HR positive breast cancers, with over 50% of patients relapsing in the first 3 to 5 years and metastatic TNBC patients having a median overall survival of less than a year. Due to the poor prognosis and high relapse rate of TNBC, it is imperative to develop new and effective drug candidates for these patients." stated Kishor Bhatia, Ph.D., Lantern’s Chief Scientific Officer.

The SABCS poster highlights new preclinical results demonstrating LP-184’s potent in vitro and in vivo anti-tumor efficacy across a broad range of breast cancer models, including TNBC models that are resistant to Olaparib, a PARP inhibitor (PARPi) and a current standard of care (SOC) agent for TNBC. LP-184 had low nanomolar potency (average IC50 of 297nM) when tested across a panel of 4 TNBC breast cancer cell lines. Considering LP-184’s in vitro anti-tumor activity for TNBCs, LP-184 was additionally tested in 10 patient derived xenograft (PDX) mouse models of TNBCs, 7 of which were resistant to Olaparib. In all 10 TNBC PDX models, LP-184 treatment led to complete and durable tumor regression of 107-141%.

In addition to LP-184’s preclinical anti-tumor efficacy for primary TNBC tumors, LP-184 may also have added therapeutic potential to treat brain metastases (brain mets.) from TNBCs, which are found in ~14% of TNBC patients at their initial diagnosis. LP-184 was previously shown to have anti-tumor activity in brain mets. cell lines derived from breast, lung and skin cancers, and was additionally shown to have up to 6X more in vitro anti-tumor activity in comparison to multiple brain mets. SOC agents.

"Patients with primary and secondary TNBCs are in urgent need of new and effective therapies. The combined anti-tumor potency of LP-184 in PARPi resistant TNBC PDXs and LP-184’s distinct PARP independent mechanisms, strongly support the potential of LP-184 to be added to the treatment armamentarium for TNBC patients" continued Dr. Bhatia.

A full version of the poster presentation from the SABCS conference 2022 can be found on Lantern’s website.

About LP-184:

LP-184 is a small molecule drug candidate with a synthetically lethal mechanism of action (MoA) that preferentially damages DNA in cancer cells that harbor mutations in DNA damage repair (DDR) genes and that overexpress the enzyme PTGR1. Lantern is developing LP-184 for genetically defined solid tumors including TNBC, pancreatic, and bladder, as well as several central nervous system (CNS) tumors including glioblastoma, brain mets., and atypical teratoid rhabdoid tumors (ATRT).

LP-184 has been granted Orphan Drug Designation by the FDA for the treatment of pancreatic cancer, malignant gliomas, and ATRT and was also granted a Rare Pediatric Disease Designation for ATRT. These designations and continued positive preclinical data will help to accelerate LP-184 towards a targeted IND submission in Q1 2023 and first in human Phase 1 clinical trials anticipated to commence in Q2 2023.

December 13, 2022 Calidi Biotherapeutics, Inc. (Calidi), a clinical-stage biotechnology company that is pioneering allogeneic stem cell-based platforms to revolutionize oncolytic virus immunotherapies, reported that the California Institute for Regenerative Medicine (CIRM) has awarded the company a $3.1 million grant to support continued development of the company’s Supernova-1 (SNV1) pre-clinical program through Investigational New Drug (IND) application (Press release, Calidi Biotherapeutics, DEC 13, 2022, View Source [SID1234625195]). In addition, CIRM has awarded City of Hope a $12 million grant to fund a Phase 1 physician-sponsored clinical trial evaluating Calidi’s licensed oncolytic virotherapy NeuroNova platform in patients with recurrent high-grade glioma, a form of advanced brain cancer.

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The first grant was awarded to Calidi to support IND-enabling studies, finalize manufacturing, and the completion of Calidi’s IND application for the SNV1 program. SNV1 is composed of allogeneic, adipose-derived mesenchymal stem cells (AD-MSC) loaded with the oncolytic vaccinia virus Cal1, targeting a variety of solid tumors including metastatic/unresectable melanoma, triple negative breast cancer, and advanced head and neck squamous cell carcinoma. Calidi’s research has shown the potential ability of SNV1 to shield the viral payload from the immune system, supporting efficient delivery to tumor sites and effectively potentiating oncolytic viruses. A previously conducted physician-sponsored Phase 1 clinical trial using autologous adipose-derived stromal cells demonstrated excellent safety and early signs of efficacy in 24 patients with advanced solid tumors and two patients with acute myeloid leukemia (AML).

"With limited treatment options and poor survival rates, there remains a significant unmet need for the development of effective treatment options for patients suffering from metastatic/unresectable melanoma, triple negative breast cancer, and advanced head and neck squamous cell carcinoma," said Boris Minev, M.D., President, Medical and Scientific Affairs of Calidi Biotherapeutics and the principal investigator of this grant. "This generous grant from CIRM will accelerate the further development of SNV1 through our IND application and beyond."

"I have been working with an incredible team of scientists in Calidi’s research laboratories to develop this powerful off-the-shelf stem cell-based oncolytic therapy with the potential to revolutionize the treatment of solid tumors," said Antonio F. Santidrian, Ph.D., co-inventor of SNV technology and SVP, Global Head of R&D of Calidi Biotherapeutics. "We are deeply appreciative of the CIRM funding mechanism and the unanimous vote of CIRM’s independent reviewers to support the development of SNV1, which will allow us to validate the platform in a clinical setting."

The second grant was awarded to City of Hope to study the effects of multiple dose application of neural stem cells (NSC)-based oncolytic virotherapy in patients with recurrent high-grade gliomas. The study will utilize Calidi’s licensed NNV2 oncolytic virotherapy platform, a cutting-edge therapeutic candidate comprising tumor-tropic neural stem cells delivering an oncolytic adenovirus selectively to tumor sites in patients with recurrent high-grade glioma. The grant was awarded to City of Hope to support the manufacturing of the therapeutic agent, the conducting of the multi-center Phase 1 trial, and the determination of activity, biodistribution, immunogenicity, and preliminary clinical efficacy. The study received FDA authorization to proceed with a Phase 1 clinical trial, which will be led by principal investigator Jana Portnow, M.D., Professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and Co-Director of the Brain Tumor Program at City of Hope, one of the largest cancer research and treatment organizations in the United States and a founding member of the National Comprehensive Cancer Network. Calidi holds an exclusive worldwide licensing agreement for patents covering the NSC-CRAd-S-pk7 technology (NeuroNova).

"I am honored that CIRM has recognized the expertise City of Hope has in early-phase development of leading-edge therapies for brain tumors," Portnow said. "Our research portfolio has piloted multiple innovative strategies to fight brain cancer, including the use of neural stem cells that act as homing devices to deliver therapies directly to tumors in the brain."

"I am delighted by the grant awarded to our collaborators at City of Hope for the treatment of recurrent brain tumors in adults. We believe our neural stem cell-mediated virotherapy has the potential to drive improved clinical outcomes for patients with high grade gliomas. Given NNV2’s ‘off-the-shelf’ nature, this therapy will be lower cost than autologous cell-based therapies and could be rapidly made available, bringing value to the healthcare system, and providing diverse patient populations access to treatment," said Calidi Biotherapeutics CEO and Chairman of the Board Allan J. Camaisa. "We are pleased to receive the support of CIRM and the further endorsement of our NeuroNova platform and are excited for the continued advancement of this Phase 1 study with our partners at City of Hope."