Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of … – The Bakersfield Californian

Off-the-Shelf CAR T-cell Product Candidate Derived from Clonal Master iPSC Line with Novel CD19-specific 1XX CAR Integrated into TRAC Locus

Phase 1 Clinical Study will Evaluate Three Dosing Regimens of FT819 for Patients with Advanced B-cell Leukemias and Lymphomas

SAN DIEGO, Aug. 02, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, announced today that the first patient has been treated with FT819, an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy targeting CD19+ malignancies. FT819 is the first-ever CAR T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line, a renewable cell source that enables mass production of high quality, allogeneic CAR T cells with greater product consistency, off-the-shelf availability, and broader patient accessibility. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy.

Remarkable clinical outcomes have been achieved through treatment with patient-derived CAR T-cell therapy, however, next-generation approaches are necessary to reach more patients who are in need of these highly-effective therapies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. Treatment of the first-ever patient with FT819 ushers in a new era for off-the-shelf CAR T-cell therapy, with the potential to overcome the real-world limitations of existing patient- and donor-derived therapeutic approaches and unlock the full potential of CAR T-cell therapy. We would like to thank our collaborators at Memorial Sloan Kettering Cancer Center, whose partnership over the past five years has profoundly contributed to this landmark achievement.

FT819 was designed to specifically address several limitations associated with the current generation of patient- and donor-derived CAR T-cell therapies. Under a collaboration with Memorial Sloan Kettering Cancer Center (MSK) led by Michel Sadelain, M.D., Ph.D., Director, Center for Cell Engineering and Head, Gene Expression and Gene Transfer Laboratory, the Company incorporated several first-of-kind features into FT819 including:

Use of a clonal master engineered iPSC line as the starting cell source, which enables CAR T cells to be mass produced and delivered off-the-shelf for broad patient access;Incorporation of a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion as described in the journal Nature Medicine (

);Insertion of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR expression and enhanced T-cell potency as described in the journal Nature (https://

); andComplete bi-allelic disruption of T-cell receptor (TCR) expression for the prevention of graft-versus-host disease (GvHD), a potentially life-threatening complication associated with allogeneic T-cell therapy.

The multi-center Phase 1 clinical trial of FT819 is designed to determine the recommended Phase 2 dose and schedule of FT819 and assess its safety and clinical activity in adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-cell lymphomas (BCL). Three treatment regimens will be independently evaluated for each type of malignancy in dose escalation: Regimen A as a single dose of FT819; Regimen B as a single dose of FT819 with IL-2 cytokine support; and Regimen C as three fractionated doses of FT819. For each indication and regimen, dose-expansion cohorts may be enrolled to further evaluate the clinical activity of FT819. The first patient with relapsed / refractory ALL was enrolled in Regimen A and received a dose of 90 million cells.

At the 24th American Society of Gene & Cell Therapy Annual Meeting held in May 2021, the Company presented preclinical data demonstrating that FT819 exhibits uniform 1XX CAR expression with complete elimination of endogenous TCR expression. The product candidate was shown to contain a stem- and central-memory T-cell phenotype, and had high-level expression of the activation marker CD25 and the trafficking marker CXCR4 and very low-level expression of the checkpoint proteins PD1, TIM3, CTLA4 and LAG3. Additionally, data from functional assessments showed that FT819 had potent antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of healthy donor-derived CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.

Pursuant to a license agreement with MSK, Fate Therapeutics has an exclusive license for all human therapeutic use to U.S. Patent No. 10,370,452, which covers compositions and uses of effector T cells expressing a CAR, where such T cells are derived from a pluripotent stem cell including an iPSC. In addition to the patent rights licensed from MSK, the Company owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

Fate Therapeutics haslicensedintellectual propertyfrom MSK on which Dr. Sadelain is aninventor.As a result of the licensing arrangement, MSK has financial interests related to Fate Therapeutics.

About Fate Therapeutics iPSC Product Platform The Companys 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 Companys 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 Companys 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.

About FT819 FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

About Fate Therapeutics, Inc. Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the advancement of, plans related to, and the therapeutic potential of the Company's product candidates, the Companys clinical development and manufacturing strategies, and the Companys plans for the clinical investigation and manufacture of its product candidates, including FT819. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, the risk that the Company may cease or delay clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact: Christina Tartaglia Stern Investor Relations, Inc. 212.362.1200 christina@sternir.com

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Fate Therapeutics Announces Treatment of First Patient in Landmark Phase 1 Clinical Trial of ... - The Bakersfield Californian

IDH1 Inhibitors, CAR T-Cell Therapy, and Third-Generation TKIs Refresh Relapsed/Refractory Leukemia Landscape – OncLive

Acute Myeloid Leukemia

Historical complete response (CR)/CR with incomplete hematologic recovery rates with approved IDH inhibitors, enasidenib (Idhifa) and ivosidenib (Tibsovo), hover around 30% and have a median overall survival (OS) of approximately 9 months in the relapsed/refractory setting, said Shammo, a professor of medicine and pathology at Rush University Medical Center, in a virtual presentation during the2021 ASCO Direct HighlightsTMwebcast in Chicago, a program developed by Physicians Education Resource LLC.

Olutasidenib, a highly potent, orally active, selective IDH1 inhibitor, was developed to improve outcomes in the 7% to 14% of patients with AML who harbor IDH1 mutations.

In the phase 1/2 2102-HEM-101 trial (NCT02719574), 150 mg of oral olutasidenib was evaluated as a single agent and in combination with azacitidine across 8 cohorts of patients with acute myeloid leukemia (AML) and myelodysplastic syndromes. Findings from the planned interim analysis, which were presented during the 2021 ASCO Annual Meeting, focused on cohort 1, which enrolled 153 patients with relapsed/refractory, IDH1-mutant AML.1

In the efficacy-evaluable population (n = 123), 37% of patients had secondary AML, 73% of patients had intermediate cytogenetic risk, 44% of patients were refractory to their last line of therapy, and 11% had failed allogeneic stem cell transplant, reflecting a difficult population to treat, said Shammo.

The primary end point, CR/CR with partial hematologic recovery (CRh), was 33% (95% CI, 25.1%-42.4%), and most CR/CRh responders had a CR (30%; 95% CI, 22.1%-39.0%).

Transfusion independence was achieved in all response groups, particularly those achieving a CR, said Shammo.

The agent also demonstrated durable CR/CRh benefit, with a median duration of CR/CRh that was not reached and a median duration of response (DOR) of 11.7 months. In a sensitivity analysis with transplant considered as the end of a response, the median duration of CR/CRh response was 13.8 months.

Those who responded well had a much longer DOR, and a fraction of those patients managed to go onto stem cell transplant, which is what you would like to do in relapsed/refractory AML, said Shammo.

Better response was strongly associated with longer survival as well. At a median follow-up of 9.7 months, the median OS was not reached in patients who had achieved a CR/CRh, with an estimated 18-month OS rate of 87%. In the safety population (n = 153), the median OS was 10.5 months (95% CI, 7.7-15.5). Among nonCR/CRh responders and non-responders, the median OS was 15.0 months (95% CI, 5.0not evaluable) and 4.1 months (95% CI, 3.2-5.8), respectively.

Clinical benefit, as evidenced by DOR and OS, extended to patients who responded but did not achieve CR/CRh, said Shammo.

The primary treatment-emergent adverse effects (AEs) included leukocytosis (all-grade, 25%; grade 3/4, 9%) and febrile neutropenia (all-grade, 22%; grade 3/4, 20%), said Shammo. AEs of special interest reflected reports of differentiation syndrome (all-grade, 14%; grade 3/4, 7%), QTc prolongation (all-grade, 8%; grade 3/4, <1%), and liver abnormalities (all-grade, 21%; grade 3/4, 10%).

Olutasidenib was well tolerated with a safety profile largely consistent with that of other IDH inhibitors, but patients should be monitored for differentiation syndrome and liver abnormalities, said Shammo.

These results are very promising and very impressive, and, hopefully, we will see more results not only with the single agent but also with the combination with azacitidine in other myeloid malignancies, added Shammo.

Turning to acute lymphoblastic leukemia (AML), Shammo discussed the results of the phase 1/2 ZUMA-3 trial (NCT02614066), which evaluated the CD19-directed chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel in patients with relapsed/refractory ALL.2

Approximately 40% to 50% of adults with B-ALL experience relapse after initial treatment, with a 1-year OS rate of 26% after first salvage therapy, said Shammo in explaining the rationale for the study.

In the phase 1 portion of the study, brexucabtagene autoleucel demonstrated a CR/CRi rate of 83% and manageable safety profile. In the phase 2 portion, 71 patients were enrolled, and 55 patients received brexucabtagene autoleucel.

Patients could have received prior treatment with blinatumomab (Blincyto) and underwent conditioning chemotherapy with fludarabine and cyclophosphamide prior to treatment with the recommended phase 2 dose of brexucabtagene autoleucel: 1 x 106 CAR T cells/kg.

Brexucabtagene autoleucel was successfully manufactured in 92% of patients, and the median time from leukapheresis to manufacturing release was 13 days for patients in the United States, which Shammo called remarkable.

Regarding baseline demographics, 27% of patients had Philadelphia chromosomepositive disease, 100% of which had central nervous system disease at baseline, and 47% of patients had received at least 3 lines of prior therapy.

Additionally, 45% of patients received prior blinatumomab, 42% underwent prior allogeneic transplant, and the median blast count was 65.0 and 59.0 at screening and preconditioning after bridging chemotherapy, respectively.

At a median follow-up of 16.4 months, the primary end point of CR/CRi rate by central assessment, was 70.9% (CR, 56.4%; CRi, 14.5%); 31% of responders were in ongoing remission at the data cutoff.

[We saw] a high and durable response rate in heavily pretreated adults with relapsed/refractory B-ALL, most of whom had high disease burden, said Shammo.

The median time to initial CR/CRi was 1.1 months. The minimal residual disease (MRD)negativity rate was 97% in responders, and 10 patients, including 9 with CR/CRi and 1 with blast-free hypoplastic or aplastic bone marrow underwent allogeneic transplant a median of 98 days (range, 60-207) following CAR T-cell infusion.

This is exactly what you would like to do: induce patients into remission to take them to allogeneic transplant, said Shammo. Whats remarkable is that MRD negativity in patients who had this treatment approximated 100%.

Among patients with CR/CRi (n = 39), the median OS was not reached (95% CI, 16.2-NE) and the median relapse-free survival (RFS) was 14.2 months (95% CI, 11.6-NE). All-treated patients (n = 39) had a median OS and RFS of 18.2 months (95% CI, 15.9-NE) and 11.6 months (95% CI, 2.7-15.5) respectively. Non-CR/CRi responders (n = 16) had a median OS and RFS of 2.4 months (95% CI, 0.7-NE) and 0.0 months (95% CI, NE-NE), respectively.

Regarding safety, any-grade cytokine release syndrome (CRS) occurred in 89% of patients, and grade 3 or higher CRS occurred in 24% of patients, with a median onset of 5 days and manifestation of pyrexia and hypotension.

Thats relatively favorable compared with what you might expect with [CAR T-cell therapy], said Shammo.

No cases of grade 5 CRS were reported, although 1 patient had grade brain herniation related to study treatment.

Any-grade neurologic events were reported in 60% of patients, and grade 3 or greater events occurred in 25% of patients, with a median onset of 9 days and manifestation of tremor and confused state.

Tocilizumab (Actemra), steroids, and vasopressors were given to 80%, 75%, and 40% of patients, respectively.

The safety profile was manageable, and AEs were largely reversible, said Shammo. The efficacy, rapid manufacturing, and manageable safety support the promising potential of brexucabtagene autoleucel to provide long-term clinical benefit in adults with relapsed/refractory B-ALL.

On April 2, 2021, a supplemental biologics license application was submitted to the FDA for brexucabtagene autoleucel as a treatment for adult patients with relapsed/refractory B-cell precursor ALL.3

If approved, brexucabtagene autoleucel would become the first and only CAR T-cell therapy approved for adults aged at least 18 years old with relapsed/refractory ALL.

The final study Shammo highlighted was the phase 2 OPTIC trial (NCT02467270), which evaluated 3 daily starting doses of ponatinib45 mg (n = 93), 30 mg (n = 93), and 15 mg (n = 91)in patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to a prior second-generation BCR-ABL1 TKI inhibitor or with a T315I mutation.4

Patients in the 45-mg and 35-mg arms were dose reduced to 15 mg daily upon achievement of 1% or less BCR-ABL1 and across arms were dose reduced to 10 mg daily in the presence of AEs.

Ponatinib, the only pan-BCR-ABL1 inhibitor, is a third-generation TKI designed to inhibit BCR-ABL1 with or without any single resistance mutation, including T315I.

In the pivotal, phase 2 PACE trial (NCT01207440), ponatinib demonstrated deep and durable responses to 45 mg of ponatinib in patients with resistant and intolerant CP-CML. However, a high incidence of arterial occlusive events (AOEs) was reported in the study, thought to be dose dependent, which ultimately compromised the utility of the drug, said Shammo.

[OPTIC] asked what dose is needed to be sure that the patients disease is under control and that perhaps we had mitigated the AOEs, said Shammo.

Notably, more than half of patients across dose cohorts had received at least 3 prior TKIs, and approximately a quarter of patients had a T315I mutation, said Shammo.

At a median follow-up of 32 months, the percentage of patients with 1% or less BCR-ABL1 at 12 months was 44.1% (95% CI, 31.7%-57.0%), 29.0% (95% CI, 18.4%-41.6%), and 23.1% (95% CI, 13.4%-35.3%) in the 45-mg, 30-mg, and 15-mg cohorts, respectively.

In the 30-mg and 15-mg cohorts, patients with less-resistant disease and without a T315I mutation at baseline had greater benefit than those with [a] T315I [mutation], said Shammo.

The 3-year OS probabilities were very reasonable, said Shammo, at 89.29%, 88.58%, and 91.71%, respectively. Notably, robust survival outcomes were reported in patients with and without BCR-ABL1 mutations, said Shammo.

What was interesting is that if you had the T315I mutation at baseline, you do need the 45-mg dose, because the response rates [with that dose] seem to be so much better than [those] patients who received a lower dose of ponatinib, said Shammo.

In terms of safety, any-grade treatment-emergent AOEs occurred in 9.6% of patients in the 45-mg arm, 5.3% in the 30-mg arm, and 3.2% in the 15-mg arm; grade 3 or greater rates occurred in 5.3%, 5.3%, and 3.2% of patients, respectively.

At this primary analysis, novel response-based ponatinib dosing regimens had clinically manageable safety and AOE profiles, with an optimal benefit-risk profile achieved with a 45-mg starting dose reduced to 15 mg upon response, concluded Shammo.

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IDH1 Inhibitors, CAR T-Cell Therapy, and Third-Generation TKIs Refresh Relapsed/Refractory Leukemia Landscape - OncLive

Lenzilumab Treatment May Provide Enhanced Likelihood of Survival Without Ventilation in Hospitalized Black and African-American COVID-19 Patients -…

BURLINGAME, Calif.--(BUSINESS WIRE)--Humanigen, Inc. (Nasdaq: HGEN) (Humanigen), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called cytokine storm, announced analysis of results from its Phase 3 LIVE-AIR study of lenzilumab in hospitalized patients with COVID-19 suggesting Black and African-American patients having a CRP<150 mg/L may be the highest responders to treatment, with a nearly 9-fold increase in likelihood of survival without ventilation (SWOV) [n=51, p-value=0.0412]. In the overall population with CRP<150 mg/L, LIVE-AIR Phase 3 results show patients treated with lenzilumab demonstrated a 2.5-fold increased likelihood of SWOV [mITT, n=351, p-value=0.0009].

Humanigen believes this analysis is an important finding because Black and African-American patients are hyper-vulnerable to COVID-19, said Cameron Durrant, MD, Chief Executive Officer, Humanigen. In light of the rapid ongoing spread of the Delta variant, data suggesting that Black and African-American patients, who are hyper-vulnerable to COVID-19, and may be hyper-responsive to lenzilumab is important in the broader context of the potential benefits that may result if the FDA were to grant emergency use authorization.

The Centers for Disease Control and Prevention (CDC) has found that race and ethnicity are risk markers for other conditions that affect health, including socioeconomic status, access to health care, and exposure to SARS-CoV-2 related to occupation, such as frontline, essential, and critical infrastructure workers.1 The American Heart Associations COVID-19 Cardiovascular Disease Registry found that Black patients had the highest prevalence of obesity, hypertension, and diabetes, all of which are medical conditions the CDC identifies as making adults of any age more likely to get severely ill from COVID-19.3,4

In the interest of public health and safety, it is our priority to share data with stakeholders to improve our understanding of the disease and potential treatments, said Adrian Kilcoyne, MD, Chief Medical Officer, Humanigen. While there may be some limitations to subset analyses, we believe the ongoing public health crisis caused by SARS-CoV-2 warrants consideration of these important data by regulatory authorities.

Humanigen intends to submit data from this analysis for publication in a peer-reviewed journal and present the findings at a medical meeting. These new data from the LIVE-AIR study will also be shared with regulatory authorities in the US, UK, European Union, and other geographies.

About the LIVE-AIR, Phase 3 Study of Lenzilumab

LIVE-AIR Phase 3 study met its primary endpoint of survival without ventilation demonstrating a 1.54-fold improvement overall and trended to a 2.68-fold improvement in Black and African-American patients. This study was a randomized, double-blind, placebo-controlled, multi-center Phase 3 trial for the treatment and prevention of serious and potentially fatal outcomes in patients hospitalized with COVID-19 pneumonia. The primary objective was to assess whether lenzilumab, in addition to other treatments, which included dexamethasone (or other steroids) and/or remdesivir, could alleviate the immune-mediated cytokine storm and improve survival without ventilation, or SWOV (sometimes referred to as ventilator-free survival). SWOV is a composite endpoint of time to death and time to invasive mechanical ventilation (IMV), which is a robust measure that is less prone to favor a treatment with discordant effects on survival or days free of ventilation.5

The LIVE-AIR study enrolled 520 patients in 29 sites in the US and Brazil who were at least 18 years of age; experienced blood oxygen saturation (SpO2) of less than or equal to 94%; or required low-flow supplemental oxygen, or high-flow oxygen support, or non-invasive positive pressure ventilation; and were hospitalized but did not require IMV. Following enrollment, subjects were randomized to receive three infusions of either lenzilumab or placebo, each infusion separated by eight hours over a 24-hour period. The primary endpoint was the difference between lenzilumab treatment and placebo treatment in SWOV through day 28 following treatment. Key secondary endpoints, also measured through day 28, included ventilator-free days, duration of ICU stay, incidence of IMV, extracorporeal membrane oxygenation (ECMO), and/or death, time to death, all-cause mortality, and time to recovery. Results of the trial have been submitted for publication in a peer-reviewed journal.

About Humanigen, Inc.

Humanigen, Inc. (Nasdaq: HGEN) (Humanigen), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called cytokine storm. Lenzilumab is a first-in class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor (GM-CSF). Results from preclinical models indicate GM-CSF is an upstream regulator of many inflammatory cytokines and chemokines involved in the cytokine storm. Early in the COVID-19 pandemic, investigation showed high levels of GM-CSF secreting T cells were associated with disease severity and intensive care unit admission. Humanigens Phase 3 LIVE-AIR study suggests early intervention with lenzilumab may prevent consequences of a full-blown cytokine storm in hospitalized patients with COVID-19. Humanigen is developing lenzilumab as a treatment for cytokine storm associated with CD19-targeted CAR-T cell therapies and exploring the effectiveness of lenzilumab in other inflammatory conditions such as acute Graft versus Host Disease (aGvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), eosinophilic asthma, and rheumatoid arthritis. Humanigen is also developing a portfolio of clinical and pre-clinical therapies for the treatment of inflammation and immuno-oncology. For more information, visit http://www.humanigen.com and follow Humanigen on LinkedIn, Twitter, and Facebook.

Humanigen Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment, and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct, and you should be aware that actual events or results may differ materially from those contained in the forward-looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements, including, without limitation, statements regarding the effectiveness of lenzilumab in Black and African-American patients; the review of our submission for emergency use authorization by the FDA; and our other plans to explore the effectiveness of lenzilumab and other candidates in our development portfolio as therapies for other inflammation and immune-oncology indications.

Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the risks inherent in our lack of profitability and need for additional capital to grow our business; our dependence on partners to further the development of our product candidates; the uncertainties inherent in the development, attainment of the requisite regulatory authorizations and approvals and launch of any new pharmaceutical product; the outcome of pending or future litigation; and the various risks and uncertainties described in the "Risk Factors" sections of our latest annual and quarterly reports and other filings with the SEC.

All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not rely upon any forward-looking statements as predictions of future events. The Company undertakes no obligation to revise or update any forward-looking statements made in this filing to reflect events or circumstances after the date hereof or to reflect new information or the occurrence of unanticipated events, except as required by law.

Sources:

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Lenzilumab Treatment May Provide Enhanced Likelihood of Survival Without Ventilation in Hospitalized Black and African-American COVID-19 Patients -...

Is This Small-Cap Biotech a Buy After Its Second Approved Gene Therapy? – Motley Fool

Key Points

Despite recently getting its third drug approved, Bluebird Bio (NASDAQ:BLUE) only has a $1.7 billion market cap. Will the company overcome its past pricing issues and fly to new highs? And could its lead in sickle cell disease clinical trials translate into massive gains for investors?

Bluebird Bio already had a multiple myeloma CAR T-cell therapy, Abecma, approved earlier this year, and now it has not one, but two gene therapy approvals for rare genetic diseases in the EU. On July 21, the rapidly maturing biotech received EU approval for its latest gene therapy, Skysona, for cerebral adrenoleukodystrophy (CALD). This rare pediatric neurodegenerative disease affects boys, with just over 1,000 patients having been diagnosed in the U.S., and just over 6,000 in Europe. Devastating and irreversible, it worsens over time, causing deterioration of nerve cells in the brain. Most patients die within two years of diagnosis.

Before Skysona was approved, the only option available to CALD patients was a stem cell transplant -- a treatment that is less likely to cause complications if the donor is a sibling. However, it is estimated that fewer than 20% of CALD patients have a matched sibling donor.

Image source: Getty Images.

Skysona, a one-time gene therapy, has proven very effective against CALD -- 90% of patients who underwent the treatment were free from major functional disabilities at least 24 months afterward. But cost is liable to be an issue. Bluebird Bio priced its first gene therapy, Zynteglo (marketed for a different rare genetic disease, transfusion-dependent beta-thalassemia), at $1.8 million, so I expect it to price Skysona similarly. With approximately 6,000 CALD patients in Europe, that's an addressable market worth just over $10 billion.

Despite Zynteglo's great benefits for patients, Bluebird has had trouble reaching reimbursement agreements with payers for the treatment. The biotech even withdrew Zynteglo from the German market in April after it could not agree on a price with that nation's public health insurance system. There is also the question of who is diagnosing such a rare disease. In most EU countries, newborns are not screened for CALD, and in the U.S., only 20 states and the District of Columbia screen for it. Unfortunately, the lack of testing may be leaving a significant percentage of CALD patients undiagnosed.

All of this may at least be partially factoring into Wall Street's weak revenue forecasts for Skysona. One analyst at Jefferies projects peak annual sales of only $74 million for the CALD gene therapy.

While Skysona can be a life-extending therapy for CALD patients, as Zynteglo is for transfusion-dependent beta-thalassemia patients, these are incredibly rare diseases. Bluebird Bio's next target, sickle cell disease, is more common, affecting approximately 100,000 Americans and 1 out of every 365 African-American births, according to the Centers for Disease Control and Prevention. Given that its sickle cell disease treatment utilizes a lentivirus-based delivery system similar to the ones used by Zynteglo and Skysona, the company will have quite a bit of safety data to lean on when it goes to the FDA for approval of its sickle cell treatment. That's tentatively scheduled to happen in 2023.

While CRISPR-based treatments have generated a lot of hype,the sickle cell treatment utilizing CRISPR that is the most advanced in clinical trials is CTX001, which is being developed jointly by CRISPR Therapeutics (NASDAQ:CRSP) and Vertex (NASDAQ:VRTX). Thus far, they have only delivered data on seven CTX001 recipients in a phase 1/2 trial. By contrast, Bluebird Bio's sickle cell therapy has already moved into phase 3 trials after showing significant promise in its earlier-stage studies. So Bluebird Bio seems to have at least a two- to three-year lead on its CRISPR-based rivals in its efforts to get a therapy approved for this large potential market.

In a sense, Zynteglo and Skysona are warmups for Bluebird Bio as it prepares for all of the pricing issues and negotiations that will come with the massive addressable market that is sickle cell disease gene therapy. With approximately 100,000 people suffering from the disease in the U.S. alone, even at just 5% penetration, this could be a $10 billion a year opportunity. If it can approach that level of market penetration, Bluebird Bio could surge past its current market-cap peak to reach over $15 billion -- which would make it just under a 10-bagger from here. And that does not factor in the estimates for more than $1 billion in annual sales for Abecma by 2026.

Considering that Bluebird Bio currently has a market cap of $1.7 billion with just over $1 billion in cash on the books, there is a lot of potential upside here. Given its significant head start in the race to FDA approval for a sickle cell gene therapy, plus significant experience in the gene therapy field from its other endeavors, I'm rooting for this cutting-edge biotech to overcome its prior missteps and reward both patients and investors.

This article represents the opinion of the writer, who may disagree with the official recommendation position of a Motley Fool premium advisory service. Were motley! Questioning an investing thesis -- even one of our own -- helps us all think critically about investing and make decisions that help us become smarter, happier, and richer.

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Is This Small-Cap Biotech a Buy After Its Second Approved Gene Therapy? - Motley Fool

Defining Cell Culture Lines and Media – The Scientist

Cell culture is a fundamental research tool that enables scientists to probe the complexities of biology, establish drug development assays, produce recombinant proteins, and more. Choosing the most appropriate cell line to culture is often a balance between experimental need and accessibility.

Often scientists choose to culture immortalized cell lines since they offer several advantages, including perpetual growth and widespread availability. However, immortalized cells lines do not recapitulate the biology of normal healthy tissue-specific cells. Beyond the scope of investigating cancer, immortalized cell lines offer a limited purview.

In contrast, primary cells directly isolated from the tissue of interest provide a more realistic model of human health and disease because their physiology more closely resembles the healthy tissue from which they were extracted. Isolating cells from fresh human tissue is not practical for most laboratories and requires access to medical facilities or specialized approvals.

Tissue architecture is complex, comprising heterogeneous cell types in various cellular states. Purifying a homogenous population of cells from tissues requires numerous steps including specialized isolation protocols, tagging cells with cell-type-specific markers, and cell sorting. Culturing a purified population of primary cells depends on optimized cell culture media for each cell type and state.

MilliporeSigma recently partnered with PromoCell, an industry-leading manufacturer of more than 100 human cells types, to provide scientists with a broad range of ethically sourced, verified, and reliable human primary, stem, and blood cells. Each primary cell is collected from consenting donors at medical centers. Deidentified donor information, such as biological sex, age, and ethnicity for each cell line is available, enabling population-level disease modeling.

Each primary cell also undergoes stringent quality control procedures to ensure correct cellular identity, growth, and differentiation performance. PromoCell supplies a broad range of primary human cells, including chondrocytes, endothelial, epithelial, fibroblast, follicle dermal papilla, keratinocyte, melanocyte, osteoblast, pericyte, preadipocyte, and smooth muscle cells. Scientists at PromoCell validate each cell line for cell type-specific markers, cell morphology, population doubling time, and proliferation capacity. They also test the purity of each cell line to ensure the absence of HIV-1, HIV-2, HBV, HCV, fungi, mycoplasma, and other bacteria.

The idea of providing primary cells from healthy donors that are free of contamination extends to human stem and blood cells provided by MilliporeSigma and PromoCell. Adult stem and blood cells are collected from normal human bone marrow, as well as cells from umbilical cord tissue, placenta, adipose tissue, peripheral blood, and cord blood. This ensures that each stem and blood cell reflects a healthy tissue state uninfluenced by biological disease programs.

The success of cultured primary cells depends on cell-type specific optimized medium. Defined media ensures that only the desired cell type will thrive in culture. Thus, each cell line comes with optimized differentiation media systems. These systems replace serum with defined media components whenever possible, which guards against the unpredictable effects of indeterminate compounds found in serum concoctions.

For researchers who are interested in isolating cancer cells, MilliporeSigma and PromoCell provide a variety of primary cancer culture solutions. These media and reagents are optimized to selectively promote the culture of malignant cells derived from patient xenografts or primary tumors within just 4-6 weeks. Although cancer cell lines are readily available for most cancer types, they are often influenced by cell culture induced changes and do not adequately reflect the behavior of cancer in patients. MilliporeSigma and PromoCells defined serum-free formulations support the derivation of three-dimensional cancer sphere formation and ensure the highest purity of derived primary, stem, blood, and cancer cells.

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Defining Cell Culture Lines and Media - The Scientist

Preimplantation Genetic Testing Demand to Grow by 9% CAGR Annually, through 2031 – BioSpace

Preimplantation Genetic Testing Application in Embryo HLA Typing for Stem Cell Therapy will Increase, Surpassing US$ 70 Mn by 2031

The study of the preimplantation genetic testing market offers compelling insights into key factors affecting market growth trajectory. The survey report discloses insights into preimplantation genetic testing demand outlook in terms of test type, end user, application, and technology. The report also highlights the scope of preimplantation genetic testing over the forecast period

Fact.MR A Market Research and Competitive Intelligence Provider: As per a survey conducted by Fact.MR, the global preimplantation genetic testing market reached a valuation of US$ 550 million in 2020, expanding at a CAGR of 8% between 2016 and 2020.

Owing to the increase in incidence of chronic diseases and disabilities across the globe, the market for preimplantation genetic testing is estimated to surge at a robust CAGR of 9% over the forecast period 2021 to 2031.

Preimplantation genetic testing is gaining traction on the back of rising prevalence of genetic disorders among children and disabilities among the aged population. According to a study by Genetic Alliance, in the U.K., out of every 25 children, 1 child is affected by a genetic disorder and nearly 30,000 babies are diagnosed with the disease every year. Besides this, over 500 million adults and children are living with a genetic disorder in the country.

As preimplantation genetic testing is proven as an effective solution for diagnostics of genetic disorders, it is increasingly being used by healthcare providers and institutions for identifying defects present in embryos before implantation.

Thus, the need for effective diagnostic solutions to curb the rising prevalence of genetic disorders in newborns will spur the demand for preimplantation genetic testing over the coming years.

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Embryo Human leukocyte antigen (HLA) typing for stem cell therapy is anticipated to dominate the market, accounting for over 40% of the revenue share. In response to the increasing application of preimplantation genetic testing in the procedure, the segment is projected to surpass a valuation of US$ 70 million by the end of 2031.

Several healthcare institutes and research centers are increasingly investing in research & development (R&D) to find novel techniques to minimize the risks associated with the preimplantation genetic testing. Their efforts are expected to bode well for the market, creating opportunities for growth, says the Fact.MR analyst.

Key Takeaways from Preimplantation Genetic Testing Market Survey

Key Drivers

Key Restraints

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Competitive Landscape

The global market for preimplantation genetic testing is highly consolidated, where a small group of leading players are accounting for nearly half of the global sales. Key player in the landscape are focusing on engaging into strategic collaboration with other players to strengthen their market footprint. For instance,

Some of the prominent preimplantation genetic testing providers profiled by Fact.MR are:

More Valuable Insights on Preimplantation Genetic Testing Market

Fact.MR, in its new report, offers an unbiased analysis of the global preimplantation genetic testing market, analyzing forecast statistics through 2021 and beyond. The survey reveals growth projections on in the preimplantation genetic testing market with detailed segmentation:

Key Questions Covered in the Preimplantation Genetic Testing Market Report

Explore Fact.MRs Coverage on the Healthcare Domain

Genetic Testing Services Market - The future expansion of genetic testing services is heavily reliant on the advancement of information technology. Throughout the projected period, North America is expected to dominate the worldwide genetic testing services market. Increased demand for genetic testing to determine ancestry, as well as an increase in demand for in-vitro fertilization (IVF) and pre-implantation testing, are some of the primary reasons boosting market share. According to projections, the North American genetic testing market will account for over two-fifths of the total.

Rheumatoid Arthritis Stem Cell Therapy Market - Over the forecast period, the global market for rheumatoid arthritis treatments is expected to rise moderately. Over the projected period, the allogeneic mesenchymal stem cell segment is expected to lead the global rheumatoid arthritis stem cell therapy market. As the most accessible channel, hospitals are likely to account for a sizable portion of the global rheumatoid arthritis stem cell therapy market.

Serological Transplant Diagnostics Market - Serological transplant diagnosis, which is a critical component of successful and efficient organ transplantation, has grown rapidly in recent years. Growth in important distribution channels, such as hospitals and organ transplantation centres, to name a few, has boosted demand during the last five years, from 2016 to 2020, attracting more stakeholders to the business. Serological transplant diagnostic equipment sales are being fueled by an increase in incidence of serious lung, liver, and kidney disorders, as well as medical and diagnostic developments.

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Preimplantation Genetic Testing Demand to Grow by 9% CAGR Annually, through 2031 - BioSpace