Stem Cell Clinic

Researcher awarded $12 million for a stem cell trial to improve outcomes of young blood cancer patients – Stanford Medical Center Report

The California Institute for Regenerative Medicine has awarded nearly $12 million to support a clinical trial of a new cell-based treatment to improve outcomes and survival rates among children and young adults with blood cancer who receive a stem cell transplant.

The treatment, named T-allo10, aims to improve immune responses to pathogens and cancer without increasing the likelihood of graft-versus-host disease in patients who must receive a transplant from an imperfectly matched donor.

The trial will be led by Maria Grazia Roncarolo, MD, professor of pediatrics and of medicine. Roncarolo is the George D. Smith Professor of Stem Cell and Regenerative Medicine, director of the Stanford Center for Definitive and Curative Medicine and co-director of the Institute for Stem Cell Biology and Regenerative Medicine.

Every year around 500 children receive stem cell transplants in California, and while many children do well, too many experience a rejection of the transplant or a relapse of the cancer, Maria Millan, MD, president and CEO of the institute said in a press release. Finding an improved therapy for these children means a shorter stay in the hospital, less risk of the need for a second transplant, and a greater quality of life for the child and the whole family.

The current standard of care for many blood cancers is a two-part treatment of chemotherapy to destroy a patients cancer cells followed by a transplant of blood and immune stem cells from an immunologically matched donor. However, patients sometimes only have the option of receiving a transplant thats a partial immunological match, increasing the risk of graft-versus-host disease, in which the donor immune cells attack the recipients tissues. To reduce this risk, a subset of the donated cells is removed prior to transplant, which in turn increases the chance of a cancer relapse or dangerous infection.

Roncarolo and her team will test T-allo10, in which mature immune cells are concurrently administered with cells called type 1 regulatory T cells, or Tr1 cells, from the donor after a stem cell transplant. The Tr1 cells, which were originally discovered by Roncarolos team, reduce the likelihood that the donors immune cells will perceive the recipients tissue as foreign.

T-allo10 is intended to improve transplant outcomes by reducing cancer recurrence and infection rates, as well as the likelihood of graft-versus-host disease.

My team and I are thrilled to receive CIRMs support for our immunotherapy clinical trial, which may help patients with leukemia receiving a blood stem and progenitor cell transplant fromnonperfectly matched donors a population that continues to suffer poor outcomes and that has high unmet need, Roncarolo said. T-allo10 is unique, as it contains both Tr1 cells, which prevent graft-versus-host disease and rejection, and cells that can fight infections and eliminate residual cancer cells in a single cell product. The development from the bench to the bedside of a Tr1 cell-based product to improve the outcomes of stem cell transplant and induce tolerance is a shining example of the cutting-edge translational work conducted at the Stanford Center for Definitive and Curative Medicine.

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Researcher awarded $12 million for a stem cell trial to improve outcomes of young blood cancer patients - Stanford Medical Center Report

Vaccines less effective at protecting against severe COVID-19 in immunocompromised adults – EurekAlert

INDIANAPOLIS -- New real-world evidence gathered by the U.S. Centers for Disease Control and Prevention (CDC) shows that COVID-19 vaccines are less effective at protecting against COVID-19-associatedhospitalizations in people who are immunocompromised.

In general, immunocompromised individuals are at an increased risk for severe COVID-19 outcomes.

These findings indicate thatwhile two-doses of mRNA COVID-19 vaccines are beneficial inimmunocompromised individuals, theyaresignificantlyless protected from severe disease than people with normal immune systems, said study lead author PeterEmb, M.D., M.S., Regenstrief Institute president and chief executive officer andassociate dean for informatics and health services research at theIndiana UniversitySchool of Medicine. Since they are less protected after a two-dose series, those who are immunocompromisedshould receive an additional dose and a booster, take additional precautions like masking when in public, and, if they get infected, they should seek treatment with proven therapies that can protect against progression to severe disease and the need for hospitalization.

The research team gathered data from more than 89,000 hospitalizations across nine states, making this the largest study of its kind evaluating COVID-19 vaccine effectiveness among immunocompromised people. Data analyses showed that mRNA vaccines (manufactured by Pfizer andModerna) were 90 percent effective at protecting against COVID-related hospitalization in immunocompetent individuals, whereasthey wereonly 77 percent effective in those with suppressed immunity due to a range of health conditions. The differences were similar across age groups. However, the effectiveness varied greatly amongimmunocompromisedsubgroups. For example, it was lower in organ or stem cell transplant patients and better in people with rheumatologic or inflammatory disorders.

Thedata camefrom theVISION Network,a collaboration between the CDC andseven organizationswith integrated medical, laboratory and vaccination records. The network was established to assessthe effectiveness of COVID-19 vaccines.In addition to Regenstrief Institute, other members are Columbia University Irving Medical Center, HealthPartners, Intermountain Healthcare, Kaiser Permanente Northern California, Kaiser Permanente Northwest and University of Colorado.

The paper,Effectiveness of Two-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults nine states, JanuarySeptember 2021, is published in the CDCs Morbidity and Mortality Weekly Report.

Dr.Embis the first author. Other authors from Regenstrief and IU are Shaun Grannis, M.D., M.S.; Brian Dixon, PhD, MPA; William F. Fadel, PhD andNimish R.Valvi, DrPH.

Other authors on the paper areMatthew E. Levy, PhD, ofWestat; Allison L.Naleway, PhD, of Kaiser Permanente Northwest; Palak Patel, MBBS, of the CDC COVID-19 Response Team;ManjushaGaglani, MBBS, of Texas A&M University; Karthik Natarajan, PhD, of Columbia University and New York Presbyterian Hospital; KristinDascomb, M.D., PhD, of Intermountain Healthcare;ToanC. Ong, PhD, of University of Colorado; Nicola P. Klein, M.D., PhD, of Kaiser Permanente Northern California; I-Chia Liao,MPH, of Texas A&M University;JungmiHanof Columbia University; EdwardStenehjem, M.D., of Intermountain Healthcare; Margaret M. Dunne, MSc, ofWestat; Ned Lewis, MPH, of Kaiser Permanente Northern California;Stephanie A. Irving, MHS, ofKaiser Permanente Northwest; Suchitra Rao, MBBS, of University of Colorado; Charlene McEvoy, M.D., of HealthPartners Institute; Catherine H.Bozio, PhD, of the CDC COVID-19 Response Team;KempapuraMurthy, MBBS, of Texas A&M University; Nancy Grisel, MPP, of Intermountain Healthcare; Duck-HyeYang, PhD, ofWestat; Kristin Goddard, MPH, of Kaiser Permanente Northern California; Anupam B. Kharbanda, M.D., of Childrens Minnesota; Sue Reynolds, PhD, of the CDC COVID-19 Response Team; ChandniRaiyani, MPH, of Intermountain Healthcare; JulieArndorfer, MPH, of Intermountain Healthcare; Elizabeth A. Rowley, DrPH, ofWestate; Bruce Fireman, M.A., of Kaiser Permanente Northern California; JillFerdinands, PhD, of the CDC COVID-19 Response Team; Sarah W. Ball, ScD, ofWestat;OussenyZerbo, PhD. Of Kaiser Permanente Northern California; Eric P. Griggs, MPH, of the CDC COVID-19 Response Team; Patrick K. Mitchell, ScD, ofWestate; Rachael M. Porter, MPH, of the CDC COVID-19 Response Team; Salome A.Kiduko, MPH, ofWestat;LeneeBlanton, MPH, of the CDC COVID-19 Response Team; Yan Zhuang, PhDofWestat; Andrea Steffens, MPH, of the CDC COVID-19 Response Team; Sarah E. Reese, PhD, ofWestat; Natalie Olson, MPH, of the CDC COVID-19 Response Team; Jeremiah Williams, MPH, of the CDC COVID-19 Response Team; Monica Dickerson, MPH,of the CDC COVID-19 Response Team; Meredith McMorrow, M.D.of the CDC COVID-19 Response Team; Stephanie J.Schrag, DPhil,of the CDC COVID-19 Response Team; Jennifer R.Verani, M.D.of the CDC COVID-19 Response Team; Alicia M. Fry, M.D.of the CDC COVID-19 Response Team; EduardoAzziz-Baumgartner, M.D.of the CDC COVID-19 Response Team; Michelle A. Barron, M.D., of the University of Colorado; Mark G. Thompson, PhD,of the CDC COVID-19 Response TeamandMalini B. DeSilva, M.D. of HealthPartners Institute.

About Regenstrief Institute

Founded in 1969 in Indianapolis, theRegenstrief Instituteis a local, national and global leader dedicated to a world where better information empowers people to end disease and realize true health. A key research partner to Indiana University, Regenstrief and its research scientists are responsible for a growing number of major healthcare innovations and studies. Examples range from the development of global health information technology standards that enable the use and interoperability of electronic health records to improving patient-physician communications, to creating models of care that inform practice and improve the lives of patients around the globe.

Sam Regenstrief, a nationally successful entrepreneur from Connersville, Indiana, founded the institute with the goal of making healthcare more efficient and accessible for everyone. His vision continues to guide the institutes research mission.

About IU School of Medicine

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

AboutPeterEmb, M.D., M.S.

In addition to serving as the president and CEO of Regenstrief Institute, PeterEmb, M.D., M.S. is the LeonardBetleyProfessor of Medicine and associate dean for informatics and health services research at Indiana University School of Medicine, associate director of informatics with Indiana Clinical andTranslational Sciences Institute and vice president for Learning Health Systems with Indiana University Health.

Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19Associated Hospitalizations Among Immunocompromised Adults Nine States, JanuarySeptember 2021

2-Nov-2021

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Vaccines less effective at protecting against severe COVID-19 in immunocompromised adults - EurekAlert

Heart Tissue in a Dish Reveals New Links Between Neurodegeneration and Heart Disease – PRNewswire

Some cases of heart failure have root causes surprisingly similar to diseases like Alzheimers, Huntingtons and ALS.

Over time, sometimes quite rapidly, the heart's thick strong muscle tissue becomes thin and weak, causing the left ventricle to swell like a balloon. This makes the heart less able to squeeze efficiently, which can lead to blood clots, irregular heartbeats, and sometimes sudden death when the malfunctioning heart simply stops beating. The origins of cardiomyopathy are diverse, including viral infections, autoimmune diseases, toxic drug exposures, and dozens of gene mutations.

Now, a multi-disciplinary team of clinicians and researchers has deciphered the function of a specific genetic mutation that causes cardiomyopathy. Their findings,published Nov. 3, 2021, in Nature Communications, were made possible by growing gene-edited human heart tissue from induced pluripotent stem cells and measuring the activity, location and binding of this mutant protein.

The team was led by co-corresponding authors Charles Murry, MD, PhD, a regenerative medicine expert at the University of Washington; Bruce Conklin, MD, a genetic engineering expert with the Gladstone Institutes in California, and Nathan Salomonis, PhD, a computational genomics expert at Cincinnati Children's.

"We hope this study will lead to broader insights that could lead to improved heart failure therapies," Conklin says.

Cutting-edge experiments expose more of the heart's inner workings

Over the last several decades, the research community has made many discoveries that have led to improved medications and medical devices that can dramatically extend life by slowing down the progression of heart failure. However, we still lack proven cures.

This study reveals a new mechanism of cardiomyopathy initiation by the RNA binding motif protein 20 (RBM20). This protein helps control RNA splicing in the heart, the process by which RNAs are sliced and diced to give rise to different proteins in different tissues. Normally, RBM20 splices RNAs to make proteins that enable the heart to adapt to stress and contract regularly throughout a person's entire life. But a class of mutations in RBM20 result in severe cardiomyopathy in adulthood.

"We and others had previously studied RBM20's function during heart development, but we had little to no clue of why it stops working in disease. We needed to step up our game if our research was to have a clinical impact," says Alessandro Bertero, PhD, who contributed to the work while at the University of Washington and now leads an Armenise-Harvard Laboratory at the University of Turin in Italy.

Discovering this protein's role was especially complex because knocking out this gene in animal models does not mimic the damaging effects seen in people. Instead, the work required editing the genome of healthy cells and engineering human heart tissue from these cells in a lab dish. Only by producing heart tissue similar to that found in humans could the authors understand the contractile defects and molecular mechanisms underlying this gene's function in a controlled manner.

"That was exactly what we intended when we started this project by genome-editing induced pluripotent stem cells," says co-leading author Yuichiro Miyaoka, PhD, of the Tokyo Metropolitan Institute of Medical Science.

First, the team observed that the engineered muscle tissue carrying the mutant form of RBM20 did not function like tissue engineered with normal RBM20 or lacking the protein all together. The mutated muscle fibers contracted with significantly less force and upstroke velocity, much like a heart affected by cardiomyopathy.

Then, at the single-cell level, the team detected another important clue. Normally, RBM20 is located exclusively within the cell nucleus. However, the mutated form localizes almost entirely out of the nucleus, in the cell's cytoplasm.

This, by itself, did not mean muchuntil the cell was exposed to heavy stress. When that occurred, the mutant protein was detected within tiny "stress granules" made of protein and RNA that cells rapidly produce as a reaction to stress. In contrast, RBM20 in healthy cells remained within the nucleus and distinct from stress granules. This suggests there are additional cellular mechanisms, along with changes in splice-activity, leading to RBM20 cardiomyopathy.

"When the RNA binding landscape of mutant RBM20 was revealed by a technology called enhanced CLIP, it mimicked the binding of other splicing factors that have been implicated in neurodegenerative diseases. These factors, when mutated, also change their activity from RNA splicing to RNA aggregation outside the nucleus," says co-author Gene Yeo, PhD, MBA, a member of the Department of Cellular and Molecular Medicine at the University of California San Diego.

"Over time, such aggregates play havoc with other cell functions, ultimately leading to the tissue-weakening of heart muscle during cardiomyopathy," Salomonis says.

"It is intriguing to note the parallels between our observations with RBM20 and recent findings in neuro-degeneration," the paper states. "Indeed, recent work has hypothesized cytoplasmic RBM20 may be similar to the cytoplasmic RNP granules associated with neurodegeneration (Schneider et al., 2020), such as TAU for Alzheimer s disease, Huntingtin for Huntington s disease, and FUS for amyotrophic lateral sclerosis (ALS)."

Next steps

Co-authors for this study also included scientists from the University of Cincinnati Department of Electrical Engineering and Computer Science, Sana Biotechnology, and the University of California San Francisco.

The co-authors say the 3D heart tissue model they've developed has the potential to be used to test new drugs to block the formation of cytoplasmic granules as a possible treatment for cardiomyopathy, even those without RBM20 mutations.

"RBM20 has been a frustrating protein to study, as animal models don't fully recapitulate human disease pathology," says lead author Aidan Fenix, PhD. "It's exciting to now have an in vitrohuman cell model of RBM20 cardiomyopathy that shows the major clinical feature of dilated cardiomyopathy--reduced contractile force. We hope these models will speed the discovery of therapies to treat RBM20 dilated cardiomyopathy."

About this study

This work was supported by grants from the National Heart, Lung, and Blood Institute (U01 HL099997, P01 HL089707, R01 HL130533, F32 HL156361-01, HL149734, R01 HL128362, R01 HL128368, R01 HL141570, R01 HL146868); the National Institute of Diabetes and Digestive and Kidney (U54DK107979-05S1); the National Science Foundation (NSF CMMI-1661730); a JSPS Grant-in-Aid for Young Scientists, and grants from NOVARTIS, the Mochida Memorial Foundation, SENSHIN Medical Research Foundation, Naito Foundation, Uehara Memorial Foundation, a Gladstone-CIRM Fellowship, and the A*STAR International Fellowship.

SOURCE Cincinnati Children's Hospital Medical Center

http://www.cincinnatichildrens.org

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Heart Tissue in a Dish Reveals New Links Between Neurodegeneration and Heart Disease - PRNewswire

Coherus BioSciences Announces CMS Has Extended Enhanced Medicare Reimbursement for UDENYCA in the 340B Hospital Setting Through Year-End 2022 -…

REDWOOD CITY, Calif., Nov. 05, 2021 (GLOBE NEWSWIRE) -- Coherus BioSciences(Coherus, Nasdaq: CHRS), today announced that the Centers for Medicare & Medicaid Services (CMS) will continue to provide increased Medicare reimbursement in the 340B outpatient hospital setting through year-end 2022 for 28 drugs, biologics and devices impacted by the COVID-19 public health emergency, including UDENYCA (pegfilgrastim-cbqv).

We applaud CMS for continuing its support for patients, providers and hospitals impacted by the COVID-19 pandemic, said Denny Lanfear, CEO of Coherus.

After transitional pass-through payment status expires for UDENYCA on March 31, 2022,CMS will provide a separate payment through the end of 2022 to maintain the same reimbursement levels for UDENYCA in the 340B outpatient hospital setting as determined through the pass-through payment program.Pass-through payment status was established by Congress to incentivize access for Medicare patients to biosimilars and other important therapeutics and devices in the hospital outpatient setting. Under the program, reimbursement for UDENYCA in the 340B hospital outpatient setting is calculated at the CMS Average Sales Price (ASP) for UDENYCA plus 6% of the ASP for Neulasta (pegfilgrastim). By comparison, Neulasta is currently reimbursed in the 340B hospital setting at the Neulasta ASP less 22.5%.

About UDENYCA UDENYCA is the #1 prescribed pegfilgrastim pre-filled syringe in the United States.

UDENYCAis a leukocyte growth factor indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia.

Limitations of Use: UDENYCAis not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Contraindications: Patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products. Reactions have included anaphylaxis

Warnings and Precautions:

Fatal splenic rupture:Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue UDENYCAin patients with ARDS.

Serious allergic reactions, including anaphylaxis: The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue UDENYCAin patients with serious allergic reactions.

Sickle cell crises:Severe and sometimes fatal crises have occurred. Discontinue UDENYCAif sickle cell crisis occurs.

Glomerulonephritis:The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events resolved after dose reduction or discontinuation. Evaluate and consider dose-reduction or interruption of UDENYCAif causality is likely.

Leukocytosis:White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim products. Monitoring of complete blood count (CBC) during UDENYCAtherapy is recommended.

Thrombocytopenia:Thrombocytopenia has been reported in patients receiving pegfilgrastim. Monitor platelet counts.

Capillary Leak Syndrome:Has been reported after G-CSF administration, including pegfilgrastim products, and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. If symptoms develop, closely monitor and give standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells:The possibility that pegfilgrastim products act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded.

Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer:MDS and AML have been associated with the use of pegfilgrastim in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for sign and symptoms of MDS/AML in these settings.

Aortitis:Has been reported in patients receiving pegfilgrastim products, occurring as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis when signs and symptoms develop without known etiology. Discontinue UDENYCA if aortitis is suspected.

Nuclear Imaging:Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. Consider when interpreting bone imaging results.

Adverse Reactions:Most common adverse reactions ( 5% difference in incidence compared to placebo) are bone pain and pain in extremity.

To report SUSPECTED ADVERSE REACTIONS, contactCoherus BioSciencesat 1-800-4-UDENYCA (1-800-483-3692)orFDAat 1-800-FDA-1088 orwww.fda.gov/medwatch.

Full Prescribing Information available atwww.UDENYCA.com

About Coherus BioSciences

Coherus is a commercial stage biopharmaceutical company with the mission to increase access to cost-effective medicines that can have a major impact on patients lives and to deliver significant savings to the health care system. Coherus strategy is to build a leading immuno-oncology franchise funded with cash generated by its commercial biosimilar business. For additional information, please visit http://www.coherus.com.

Coherus markets UDENYCA (pegfilgrastim-cbqv) in the United States and through 2023 expects to launch toripalimab, an anti-PD-1 antibody, as well as biosimilars of Lucentis, Humira, and Avastin, if approved.

UDENYCA is a trademark of Coherus BioSciences, Inc.

Neulasta is a registered trademark of Amgen, Inc.

Avastin and Lucentis are registered trademarks of Genentech, Inc.

Humira is a registered trademark of AbbVie Inc.

Forward-Looking Statements

Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, Coherus ability to generate cash flow from its UDENYCA business; the reimbursement of UDENYCA by CMS in the 340B hospital at the rate of UDENYCA Average Sale Price + 6% of the Neulasta ASP through year-end 2022; Coherus plans to invest the cash generated by its biosimilar commercial business to build a focused immuno-oncology franchise; Coherus ability to prepare for projected launches through 2023 of toripalimab or of biosimilars of Humira, Avastin and Lucentis, if approved.

Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the risks and uncertainties inherent in the clinical drug development process; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review and the timing of Coherus regulatory filings; the risk of FDA review issues; the risk that Coherus is unable to complete commercial transactions and other matters that could affect the availability or commercial potential of Coherus drug candidates; and the risks and uncertainties of possible patent litigation. All forward-looking statements contained in this press release speak only as of the date on which they were made. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus business in general, see Coherus Annual Report on Form 10-K for the year ended December 31, 2020, filed with the Securities and Exchange Commission on February 25, 2021,its Quarterly Report on Form 10-Q for the three and six months ended June 30, 2021, filed with the Securities and Exchange Commission on August 5, 2021 and its future periodic reports to be filed with the Securities and Exchange Commission. Results for the quarter ended June 30, 2021 are not necessarily indicative of our operating results for any future periods.

Coherus Contact Information: IR Contact: Cheston Turbyfill Coherus BioSciences, Inc. IR@coherus.com

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Coherus BioSciences Announces CMS Has Extended Enhanced Medicare Reimbursement for UDENYCA in the 340B Hospital Setting Through Year-End 2022 -...

Precision BioSciences Announces Two Oral Presentations Highlighting Updated Interim Data from Lead PBCAR0191 CAR T Immunotherapy for Relapsed and…

- Enhanced Lymphodepletion Improved Overall Response Rate and Complete Response Rate Compared to Standard Lymphodepletion in Heavily Pretreated NHL and B-ALL Subjects with a Median of ~6 Prior Lines of Therapy

- Clinically Significant Activity in Subjects Previously Treated with Autologous CD19 Directed CAR T

- In B-ALL Subjects Enhanced Lymphodepletion or Higher Doses of PBCAR0191 Resulted in High Complete Response Rates Allowing the Potential to Bridge to Allogeneic Stem Cell Transplant

- Data Presented at ASH will be Updated to Include Subjects with >28 Day Follow up as of October 10, 2021

DURHAM, N.C., November 04, 2021--(BUSINESS WIRE)--Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company using its ARCUS genome editing platform to develop allogeneic CAR T and in vivo gene editing therapies, today announced that investigators involved with the Phase 1/2a study of PBCAR0191 in Relapsed/Refractory (R/R) non-Hodgkins lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL), will present new data during two oral presentations at the 63rd Annual Meeting of the American Society of Hematology (ASH) taking place December 11-14, 2021.

"We are encouraged by the response rates seen in this heavily pre-treated patient population, and that a treatment strategy with enhanced lymphodepletion mitigated PBCAR0191 rejection and improved peak CAR T cell expansion and persistence, compared to standard lymphodepletion, with predictable toxicity," said Alan List, MD, Chief Medical Officer of Precision BioSciences. "We look forward to sharing additional patient outcome, durability, and safety data for PBCAR0191 at the American Society of Hematology Annual Meeting."

The abstracts accepted by the ASH are now available at http://www.hematology.org, and will be presented during the following oral presentation sessions:

Session Name: 626, Abstract #302. Aggressive Lymphomas Prospective Therapeutic Trials: Challenging Populations Oral Presentation Title: Allogeneic CAR-T PBCAR0191 with Intensified Lymphodepletion is Highly Active in Subjects with Relapsed/Refractory B-cell Malignancies Presenting Author: Bijal Shah, M.D., Moffitt Cancer Center Date/Time: Saturday, December 11, 2021 at 4:15 PM ET Location: Georgia World Congress Center, B401-B402

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Session Name: 704, Abstract #650 Cellular Immunotherapies: Allogeneic CARs and CARs for T Cell Lymphomas Oral Presentation Title: Preliminary Safety and Efficacy of PBCAR0191, an Allogeneic Off-the-Shelf CD19-Directed CAR-T for Patients with Relapsed/Refractory (R/R) CD19+ B-ALL Presenting Author: Nitin Jain, M.D., The University of Texas MD Anderson Cancer Center Date/Time: Monday, December 13, 2021 at 10:45 AM ET Location: Georgia World Congress Center, Sidney Marcus Auditorium

Published abstracts report on key interim clinical evaluations of CD19+ NHL or B-ALL subjects treated with PBCAR0191.

Abstract #302: For 21 subjects with Relapsed/Refractory (R/R) B-cell malignancies (16 NHL, 5 B-ALL) who received PBCAR0191 following enhanced lymphodepletion1 as of July 1, 2021:

PBCAR0191 demonstrated a safety profile with no Grade 3 CRS, one Grade 3 self-limited ICANS, no evidence of GvHD, and one infectious death at Day 54, deemed possibly related to treatment.

83% (15/18) of evaluable subjects experienced a complete response (CR) rate or complete remission with incomplete marrow recovery (CRi); 62% (8/13) of NHL subjects and 80% (4/5) of B-ALL subjects, respectively.

20% (3/15) of responders demonstrated durability of response greater than 6 months, with 3 additional responders not yet having reached a 6-month evaluation threshold.

Compared to standard lymphodepletion2, enhanced lymphodepletion mitigated PBCAR0191 rejection to markedly improve peak CAR T cell expansion and persistence with area under the curve increasing 80-fold.

Among 6 subjects who progressed following prior CD19 CAR therapy (5 NHL, 1 B-ALL), the overall response rate was 83% (5/6) with 67% (4/6) achieving a CR, including an ongoing MRD negative CR in a B-ALL subject of >6 months.

Abstract #650: For 15 subjects with R/R B-cell acute lymphoblastic leukemia including 11 subjects who received PBCAR0191 Dose Level 3/4a3 and 4 subjects who received PBCAR0191 Dose Level 4b4 as of August 2, 2021:

PBCAR0191 demonstrated a safety profile with no cases of GvHD, no Grade 3 CRS, and one case of Grade 3 ICANS, which resolved within 48 hours.

For subjects who received either Dose Level 3/4a following enhanced lymphodepletion or Dose Level 4b following standard lymphodepletion, 78% (7/9) achieved a high CR or CRi rate; 56% (5/9) maintained the CR at day 28 or later potentially securing an adequate window to bridge to allogeneic stem cell transplant.

Use of enhanced lymphodepletion or higher doses of PBCAR0191 resulted in substantial improvements in peak CAR T cell expansion and area under the curve.

About Precision BioSciences, Inc.

Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS genome editing platform. ARCUS is a highly specific and versatile genome editing platform that was designed with therapeutic safety, delivery, and control in mind. Using ARCUS, the Companys pipeline consists of multiple "off-the-shelf" CAR T immunotherapy clinical candidates and several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit http://www.precisionbiosciences.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding our clinical development pipeline and interim data announcements. In some cases, you can identify forward-looking statements by terms such as "aim," "anticipate," "believe," "could," "expect," "should," "plan," "intend," "estimate," "target," "mission," "goal," "may," "will," "would," "should," "could," "target," "potential," "project," "predict," "contemplate," "potential," or the negative thereof and similar words and expressions. Forward-looking statements are based on managements current expectations, beliefs and assumptions and on information currently available to us. Such statements are subject to a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to: our ability to become profitable; our ability to procure sufficient funding and requirements under our current debt instruments and effects of restrictions thereunder; risks associated with raising additional capital; our operating expenses and our ability to predict what those expenses will be; our limited operating history; the success of our programs and product candidates in which we expend our resources; our limited ability or inability to assess the safety and efficacy of our product candidates; our dependence on our ARCUS technology; the initiation, cost, timing, progress, achievement of milestones and results of research and development activities, preclinical or greenhouse studies and clinical or field trials; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, biotechnology and agricultural biotechnology fields; our or our collaborators ability to identify, develop and commercialize product candidates; pending and potential liability lawsuits and penalties against us or our collaborators related to our technology and our product candidates; the U.S. and foreign regulatory landscape applicable to our and our collaborators development of product candidates; our or our collaborators ability to obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations and/or warnings in the label of an approved product candidate; our or our collaborators ability to advance product candidates into, and successfully design, implement and complete, clinical or field trials; potential manufacturing problems associated with the development or commercialization of any of our product candidates; our ability to obtain an adequate supply of T cells from qualified donors; our ability to achieve our anticipated operating efficiencies at our manufacturing facility; delays or difficulties in our and our collaborators ability to enroll subjects; changes in interim "top-line" and initial data that we announce or publish; if our product candidates do not work as intended or cause undesirable side effects; risks associated with applicable healthcare, data protection, privacy and security regulations and our compliance therewith; the rate and degree of market acceptance of any of our product candidates; the success of our existing collaboration agreements, and our ability to enter into new collaboration arrangements; our current and future relationships with and reliance on third parties including suppliers and manufacturers; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation relating to infringement or misappropriation of intellectual property rights; our ability to effectively manage the growth of our operations; our ability to attract, retain, and motivate key executives and personnel; market and economic conditions; effects of system failures and security breaches; effects of natural and manmade disasters, public health emergencies and other natural catastrophic events effects of the outbreak of COVID-19, or any pandemic, epidemic or outbreak of an infectious disease; insurance expenses and exposure to uninsured liabilities; effects of tax rules; risks related to ownership of our common stock and other important factors discussed under the caption "Risk Factors" in our Quarterly report on Form 10-Q for the quarterly period ended June 30, 2021, as any such factors may be updated from time to time in our other filings with the SEC, which are accessible on the SECs website at http://www.sec.gov and the Investors & Media page of our website at investor.precisionbiosciences.com.

All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we have no obligation to update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

1 eLD = Fludarabine (30 mg/m/day for 4 days) and cyclophosphamide (1000 mg/m2/day for 3 days) 2 sLD = Fludarabine (30 mg/m/day for 3 days) and cyclophosphamide (500 mg/m2/day for 3 days) 3 3 x 10 cells/kg or equivalent following either standard or enhanced lymphodepletion 4 Flat dose of 5 x 10 cells following standard lymphodepletion

View source version on businesswire.com: https://www.businesswire.com/news/home/20211104005345/en/

Contacts

Investor Contact: Alex Kelly Chief Financial Officer Alex.Kelly@precisionbiosciences.com

Media Contact: Maurissa Messier Senior Director, Corporate Communications Maurissa.Messier@precisionbiosciences.com

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Precision BioSciences Announces Two Oral Presentations Highlighting Updated Interim Data from Lead PBCAR0191 CAR T Immunotherapy for Relapsed and...

All you need to know about the COVID boosters available in Somerset County – Daily American Online

By Judy D.J. Ellich | For the Daily American

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CDC panel backs booster expansion despite concerns

Federal health officials say millions more Americans can get a COVID-19 booster and choose a different vaccine for that shot. The FDA authorized such an expansion of the nations booster campaign, also endorsed Thursday by a CDC advisory panel. (Oct. 21)

AP

Booster shots against COVID-19 are now available.

And members ofthree regional health care systems and the Cambria/Somerset COVID-19 Task Force are discussingthese vaccines, who should receive them and where to get them.

"The most important thing is that people get vaccinated, and we encourage them to do it as soon as possible," said David Bertoty, director of emergency services atUPMC Somerset. "Vaccines are safe and very effective at preventing serious illness. The vaccine is still protecting against serious illness, six to eight months after full vaccination.

"The booster reinforces the immunity that you have. For those who are immunocompromised, the booster may also be impactful if they didnt develop a response in the first place," he said.

Boosters are tobe available at UPMC Somerset's regularly scheduled clinics, which are from noon to 4:45 p.m. Mondays and Thursdays.

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UPMC Somerset is currently administering the Pfizer boosterfor immunocompromised people. Hospital officialsanticipate being able to administer the Moderna and Johnson & Johnson boosters in the near future, Bertoty said.

The health care systemrecommends that people register in advance to receive a vaccine at upmc.com. Walk-ins are also accepted.

"People should bring their vaccination cards with them so they can be updated," he said.

The Moderna and Pfizer boosters are recommended for individuals meeting the following criteria at least six months after their second dose:

The Johnson & Johnson booster has been recommended for all individuals 18 and olderat least two months after their first dose.

Chan Soon-Shiong Medical Center has administered approximately 1,500 booster doses of the Pfizer COVID-19 vaccine thus far, according to Dr. David Csikos, chief medical officer.

"Experts do not know how long someone is protected from getting sick again after recovering from COVID-19. The immunity someone gains from having an infection, called 'natural immunity,'varies from person to person. Also, the effectiveness of natural immunity against variant strains is unknown," he said."Re-infection is uncommon within 90 days following initial infection, however re-infection is possible."

"Due to the severe health risks associated with COVID-19, and the fact that re-infection is possible, patients should be vaccinated regardless of whether they have already had COVID-19 infection."

The Windber health care system provides avaccine clinic every Wednesday at the hospital. To schedule a booster dose of the Pfizer vaccine, adults are asked to call 814-467-3013.

In addition, the medical center plans to hold a Saturday vaccine clinic Nov. 13.Chan Soon-Shiong Medical Center also continues to vaccinate at schools, personal care and other facilities, including Roxbury Place and Quemahoning Towers.

COVID-19 vaccine booster shots are available for the following Pfizer vaccine recipients who completed their initial series at least 6 months ago and are:

Those who were treated for COVID-19 symptoms with monoclonal antibodies or convalescent plasma should wait 90 days before getting a COVID-19 vaccine.

Conemaugh Memorial Medical Center recently hosted two community clinics for approximately 1,000 individuals. These openings filled upquickly.

"Conemaugh Health System strongly encourages individuals who have already completed a two-dose vaccination series (Pfizer or Moderna) or the single-dose regimen (J&J/Janssen) to get their booster shot if/when they meet the specific clinical and time frame criteria," saidKristen Hudak, marketing communications director atConemaugh Health System.

"We continue to offer booster doses to our employees, and we are evaluating whether additional dates for community clinics are necessary at this time."

COVID-19 vaccinations including boosters are covered by insurance and are free to all individuals, regardless of their insured status.

Vaccine providers on the task force have encountered the following questions from local residents.

For the nearly 15 million people who got the Johnson & Johnson COVID-19 vaccine, booster shots are also recommended for those who are 18 and older and who were vaccinated two or more months ago.

The Centers for Disease Control and Prevention recommends thatthose with moderately to severely compromised immune systemsreceive an additional dose of a mRNA COVID-19 vaccine at least 28 days after a second dose of the Pfizer-BioNTech COVID-19 vaccine or Moderna COVID-19 vaccine.

Theadditional dose is intended to improve immunocompromised peoples response to their initial vaccine series. This includes people who have:

People are encouraged to talk to their health care provider about their medical condition, and whether receivingan additional dose is appropriate for them. Everyone is considered fully vaccinated two weeks after their second dose in a two-shot series or two weeks after a single-dose vaccine.

According to Jeannine McMillan, executive director of 1889 Jefferson Center for Population Health, patients need to bring their vaccination cards to an appointment for a booster shot.

If the card is lost or misplaced,contact the vaccine provider directly to access thevaccination record, she said.If the provider cannot be contacted, reach out tothe state Department of Health immunization information system at 877-774-4748.

If one hasmade every effort and still cannot locate your vaccine information, McMillan said, talk to a vaccine provider.

A full list of providers is available at http://www.vaccines.gov or by calling 1-800-232-0233 or 888-720-7489.

Some local providers numbers and websites other than the three health care systems already listed are as follows:

Total cases: 10,701.

Deaths: 253.

COVID-19 patients hospitalized: 25.

COVID-19 patients (adult) in ICU: 0.

COVID-19 patients on ventilators: 0.

Partially vaccinated: 3,093.

Fully vaccinated: 30,635.

Total cases: 19,633.

Deaths: 513.

COVID-19 patients hospitalized: 54.

COVID-19 patients (adult) in ICU: 11.

COVID-19 patients on ventilators: 11.

Partially vaccinated: 5,490.

Fully vaccinated: 62,408.

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All you need to know about the COVID boosters available in Somerset County - Daily American Online